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The Journal of Neuroscience, January 1, 1998, 18(1):388-398
Gamma Oscillations in the Entorhinal Cortex of the Freely
Behaving Rat
J. J.
Chrobak and
G.
Buzsáki
Center for Molecular and Behavioral Neuroscience, Rutgers, The
State University of New Jersey, Newark, New Jersey 07102
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ABSTRACT |
Gamma frequency field oscillations (40-100 Hz) are nested within
theta oscillations in the dentate-hilar and CA1-CA3 regions of the
hippocampus during exploratory behaviors. These oscillations reflect
synchronized synaptic potentials that entrain the discharge of neuronal
populations within the ~10-25 msec range. Using multisite recordings
in freely behaving rats, we examined gamma oscillations within the
superficial layers (I-III) of the entorhinal cortex. These
oscillations increased in amplitude and regularity in association with
entorhinal theta waves. Gamma waves showed an amplitude minimum and
reversed in phase near the perisomatic region of layer II, indicating
that they represent synchronized synaptic potentials impinging on layer
II-III neurons. Theta and gamma oscillations in the entorhinal cortex
were coupled with theta and gamma oscillations in the dentate hilar
region. The majority of layer II-III neurons discharged irregularly
but were phase-related to the negative peak of the local (layer
II-III) gamma field oscillation. These findings demonstrate that layer
II-III neurons discharge in temporally defined gamma windows
(~10-25 msec) coupled to the theta cycle. This transient temporal
framework, which emerges in both the entorhinal cortex and the
hippocampus, may allow spatially distributed subpopulations to form
temporally defined ensembles. We speculate that the theta-gamma pattern in the discharge of these neurons is essential for effective neuronal communication and synaptic plasticity in the perforant pathway.
Key words:
neuronal cooperativity; unit activity; theta waves; gamma; plasticity; Alzheimer's dementia; perforant pathway; LTP/LTD
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INTRODUCTION |
"The ultimate physical substrate
of memory formation and consolidation resides in alteration in synaptic
efficacy, which then alters the patterns of activity in large aggregate
collections of cortical neurons" (Hebb, 1949 ). It is the
modifications in the patterns of activity in large aggregate
collections of neurons that have relevance to the cognitive operations
of the mammalian brain. The means by which large collections of
neurons, within and across vast regions of the brain, can effectively
interact is not well understood.
The occurrence and transient sychronization of neurons to local field
oscillations has been demonstrated in many neural networks (Buzsáki et al., 1983, 1992; Llinás, 1988; Gray, 1989;
Steriáde et al., 1990, 1993, 1996; Murthy and Fetz, 1992; Singer,
1993; Freeman and Barrie, 1994; Fregnac et al., 1994; Bragin et al., 1995; Ylinen et al., 1995; Laurent, 1996; Laurent et al., 1996). The
local field oscillations reflect synchronized synaptic inputs that
determine neuronal discharge. The oscillations, in effect, reflect
entrainment mechanisms for timing the discharge of neurons within a
local network and, likewise, in interconnected distant networks
(Buzsáki and Chrobak, 1995).
Previously, we have described the 200 Hz synchronization of neuronal
discharge within CA1, subiculum, and the deep layers of the entorhinal
cortex in association with hippocampal sharp waves during consummatory
behavior and slow-wave sleep (Buzsáki et al., 1992; Chrobak and
Buzsáki, 1994, 1996a,b; Ylinen et al., 1995). The present study
describes a different temporal pattern, a gamma (40-100 Hz)
oscillation, that occurs within the superficial layers of the
entorhinal cortex in association with entorhinal theta waves during
exploratory behavior and rapid eye movement (REM) sleep.
Neurons within the superficial layers (II-III) of the entorhinal
cortex (EC) provide the neocortical input to the hippocampus (Steward
and Scoville, 1976; Witter and Groenewegen, 1984; Amaral and Witter,
1995). Via these neurons, the end product of neocortical associative
processes are fed into the circuitry of the hippocampus. Damage to this
population of cells is thought to be a clinical precursor to
Alzheimer's dementia and likely underlies the mnemonic deficits that
characterize the presenting symptoms of that disorder (Hyman et al.,
1984; Van Hoesen et al., 1991; Braak and Braak, 1995). Understanding
the systems physiology of this cell population should contribute to an
understanding of the mechanisms that subserve memory function and
dysfunction as instantiated in entorhinal-hippocampal circuits.
Using 16-site silicon probes to record entorhinal field potentials
concurrently across the superficial layers of this structure, we
demonstrate that oscillatory patterns in the gamma range occur nested
within theta cycles and exhibit a phase reversal zone within layer II
of the entorhinal cortex. Single-unit recordings by the 16-site probes
and single tungsten electrodes were used to demonstrate that individual
layer II-III neurons discharge in relation to the local oscillation.
Thus, the distributed population output of neurons within the
superficial layers of the EC is entrained into a theta-gamma
population rhythm.
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MATERIALS AND METHODS |
Animals and surgery. Nineteen adult Sprague Dawley
rats were used in the present experiments. For surgery, rats were
anesthetized with a ketamine mixture (4 ml/kg) consisting of (in
mg/ml): 25 ketamine, 1.3 xylazine, and 0.25 acepromazine. After a
midline scalp incision, two to four burr holes were drilled in the
skull over the hippocampal and retrohippocampal cortices. Two or three sets of four 50 µm tungsten wires were positioned into the left and
right dorsal hippocampus-subicular regions [anteroposterior (AP),
 2.5, 5.0, 7.5 mm from bregma; mediolateral (ML), 1.5, 2.5, 4.0;
dorsoventral (DV), 2-4.00 mm from the skull, according to Paxinos and
Watson (1986)] and above retrohippocampal regions (AP, 7.5-9.0; ML,
3-5.0). At least one set of hippocampal electrodes, positioned
ipsilateral to the retrohippocampal electrodes, was attached to a drive
consisting of a brass post and a single machine screw. This allowed for
optimal positioning of electrodes in the awake animal. In 15 rats, one
or two single tungsten microelectrodes (0.5-3.0 M ) mounted to
similar drives were positioned over one or two retrohippocampal areas
(AP, 7.5-9.0; ML, 3-5.0). These mounts allowed for the slow passage
of the microelectrode through the retrohippocampal region. In five
additional animals, a 16-site silicon probe (100 µm tip separations)
(Wise and Najafi, 1991; Bragin et al., 1995) was positioned via a
movable microdrive into the EC. A pair of 150 µm wires was also
positioned in the angular bundle (AP, 7.2; ML, 4.2; DV, 4.0) or CA3
region (AP, 4.0; ML, 4.0; DV, 4.0) for stimulation. Two stainless steel
watch screws driven into the bone above the cerebellum served as
indifferent (reference) and ground electrodes. Two or more additional
support screws were positioned, and the entire ensemble was secured to the skull with dental acrylic. All electrodes were attached to male
pins that were secured in a rectangular eight by four pin array and
secured with dental acrylic.
Recording of field and unit activity. Bioelectrical activity
was recorded monopolarly against the reference electrode in freely behaving rats during either movement, awake immobility, or distinct sleep stages. The animal's head stage (male pins) was connected to 24 metal oxide semiconductor field effect transistor input operational
amplifiers mounted in a female connector. The amplifiers served to
eliminate cable movement artifacts (Buzsáki, 1989). An attached
cable fed into a rotating swivel (Biela, Inc., Irvine, CA) allowed for
the free rotation of the recording cable and movement of the rodent
within a standard Plexiglas home cage or a Plexiglas open field
apparatus (50 × 50 cm). An amplifier system (Grass Neurodata
Acquisition System, Quincy, MA) and an analog-to-digital hardware-software system (EGAA; RC Electronics, Santa Barbara, CA) run
on a personal computer allowed for direct visualization and storage of
electrical activity. Wide band signals (1 Hz-0.5, 1, and 5 kHz) were
sampled at 1, 2, or typically 10 kHz and stored on optical disks.
After optimization of hippocampal microelectrodes, one or two tungsten
microelectrodes or a 16-site silicone probe was lowered through
retrohippocampal structures. Discriminable units and/or prominent
oscillations were recorded during theta states (locomotor activity and
paradoxical sleep) for 30-300 sec epochs. Typically, these epochs were
recorded interspersed with recording of hippocampal and entorhinal
sharp waves during awake immobility and slow-wave sleep epochs. Some of
the data concerning the discharge character of these neurons during
these states have been reported previously (Chrobak and Buzsáki,
1994, 1996a). When possible (depending on the stability of unit
recording), multiple continuous epochs (30-300 sec) were recorded
during both sharp waves as well as during theta. After completion of a
single pass of the movable microelectrode(s), which involved
intermittent recordings for 1-7 d, rats were anesthetized with
pentobarbital and perfused with the electrodes in situ.
Data processing and analysis. Unit activity and field
potentials were digitally filtered (120 dB/octave: unit, bandpass
0.5-5 kHz; high-frequency oscillations, bandpass 50-150 Hz) and
analyzed off-line on a 486 33 MHz and/or an IBM RS 6000 computer.
Putative single units (units typically greater than three to five times the baseline amplitude) were verified by the absence of spikes  1 msec
in autocorrelograms. Thus, amplitude discriminated spikes with
refractory periods of >1 msec were considered single units. Remaining
unit activity (units less than three times baseline and/or with
interspike intervals of <1 msec) were considered multiunit. Gamma
peaks were detected after off-line filtering (50-150 Hz) using a peak
detection algorithm.
Single-unit and multiunit activity were cross-correlated with local
entorhinal gamma peaks to determine the phase relationship between unit
activity and the local gamma field oscillation. In all
cross-correlograms, the negative peaks of the local entorhinal gamma
oscillation served as the zero reference point. Unit activity was
considered gamma-modulated if the number of events in a 10 msec time
bin (±5 msec from the zero reference) demonstrated at least a 100%
increase compared with the 10 msec time bins 45 msec before time 0 and
45 msec after time 0. Furthermore, gamma peaks within the
dentate-hilar region were cross-correlated with local entorhinal gamma
peaks to determine the synchronization between regions. Local field
averages were obtained by averaging wide-band or filtered signals using
gamma peaks or unit pulses (spike-triggered averages) as the zero
reference. The local field averages illustrate the relationship of the
local field EEG to a reference event (i.e., dentate or entorhinal theta
in relation to entorhinal gamma oscillations).
Spectral analyses and coherence were assessed from artifact-free EEG
segments. Each segment (2.54 sec) was tapered off through a Hamming
window and converted by fast Fourier transform. Power spectra were
averaged from two or four EEG segments and plotted as a function of
frequency and depth. Coherence and phase measurements were calculated
from summed values from the spectra 6-12 Hz for theta and 40-120 Hz
for gamma. Coherence was calculated for two EEG signals derived from
two electrodes on the 16-site probe. The coherence spectrum is a
measure of the statistical correlation between these two signals as a
function of frequency (Buzsáki et al., 1983; Leung and
Buzsáki 1983). Squared coherence,
K2xy, for two signals,
x and y, is equal to the average cross-power spectrum normalized by the averaged powers of the individual signals: K2xy = [Cxy]2/(Cxx
Cyy). Current source density (CSD)
was performed as described previously (Bragin et al., 1995; Ylinen et
al., 1995). Although some resistivity differences may be present in the
different cortical layers, which may influence the magnitude of sinks
and sources, in practice these are not large enough to modify the
calculated distribution of current generators significantly. The CSD
results are presented as the unscaled second derivative of voltage as a
function of depth. The exact anatomical layers corresponding to the
vertical scale of the CSD maps were reconstructed with the aid of the
histologically identified recording tracks.
Histology. Tissue was processed using either thionin
stain or a modified silver method that allows for direct visualization of damaged neurons at the electrode tip (Gallyas et al., 1990). After
completion of the experiments the rats were deeply anesthetized and
perfused through the heart first with cacodylate-buffered saline, pH
7.5, followed by a cacodylate-buffered fixative containing 4%
paraformaldehyde and 5.9% calcium chloride, pH 7.5. Brains were left
in situ for 24 hr, removed, and then post-fixed in the same
solution for 1 week. The brains were sectioned on a vibratome at 80 µm. They were dehydrated with propanol and placed in an esterifying
solution (98% propanol and 1.2% sulfuric acid) at 56°C for 16 hr.
After rehydration and sectioning they were processed according to the
following procedure: (1) pretreatment in 8% acetic acid for 10 min,
(2) washing in water for 1 min, (3) physical development with
tungstosilicic acid for ~10 min, and (4) washing in 1% acetic acid.
Finally, the sections were dehydrated, mounted on slides, and
coverslipped.
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RESULTS |
Entorhinal theta and gamma: oscillatory extracellular field
potentials occurring concurrently with hippocampal theta and gamma
Prominent theta oscillations could be observed throughout the EC
during exploratory behavior and REM sleep (Fig.
1A) that were in phase
with hippocampal theta recorded in CA1 stratum oriens and stratum
pyramidale. In association with theta, we observed a gamma oscillation
that varied between 40 and 100 Hz. The power of gamma activity, as
reflected by the area of the power between 40 and 100 Hz, was larger
during theta than in its absence in every animal investigated. When
long theta and gamma epochs, obtained during exploration (walking,
rearing, and sniffing) or during the paradoxical phase of sleep, were
subjected to spectral analysis, the increased gamma power was
distributed over a wide frequency range. On the other hand, when epochs
of similar theta frequency were selected from long records, prominent
peaks were observed in a relatively narrow gamma band (Fig.
1C). Faster theta waves were accompanied by faster-frequency
gamma peaks in the power spectra, similar to the theta-gamma
relationship in the hippocampus (Bragin et al., 1995).
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Figure 1.
Gamma and theta waves in the entorhinal cortex.
A, Depth (left) profile of entorhinal
theta waves. A 16-site silicon probe (13 most ventral sites shown) was
used to record field and unit activity concurrently at multiple laminar
sites within the entorhinal cortex. The span of the recorded area is
indicated by lines in B. Note the gradual
decrease in amplitude and phase shift of theta, which then reverses in
phase near the superficial aspect of layer II (compare trace
1 with traces 4-13). B, Image
(right) is a Nissl-stained section illustrating the
position of the 16-site recording probe within the superficial layers
of the entorhinal cortex. rs, Rhinal sulcus;
para, parasubiculum; ld, lamina
dissecans; I-V, specific lamina. C,
Power spectra of EEG extracts during different behaviors. Large peaks
at theta frequency (8-9 Hz bins) were present during RUNNING and REM sleep but not during slow
wave sleep (SWS; these peaks are cut off to emphasize
gamma power). The asterisk indicates the third harmonic
of theta frequency peak (absent during SWS). Note
similar gamma peaks during RUNNING and
REM sleep and absence of gamma frequency peak during
SWS episode. The y-scale
(POWER) is linear.
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Five animals were implanted with movable 16-site silicon probes to
record entorhinal field potentials concurrently across the superficial
layers of this structure. In confirmation of previous findings, theta
waves showed a phase-shifted dipole in the superficial layers of the EC
(Alonso and Garcia-Austt, 1987a; Mitchell and Ranck, 1980) in which
layer I theta is 180° phase-shifted compared with layer II-III.
Nested within the troughs of layer II-III theta, prominent gamma
oscillations could be observed (Figs. 2,
3). The amplitude of gamma activity was
largest in layer III. A "null zone" (i.e., amplitude minimum) and
phase reversal of gamma waves occurred near the perisomatic region of
layer II. The width of the null zone varied according to the
relationship between the penetration angle and the cytoarchitecture of
the recorded area. In four of the animals, the probe penetrated into
layer I, and we observed a polarity reversal of both theta and gamma
waves (Figs. 1, 2, 3). In the experiment shown in Figures 1 and 2, the electrode penetrated layers IV-I obliquely (Fig.
1B), and several sites recorded in and around layer
II and two sites recorded within layer I. As a result, a rather wide
reversal zone rather than a reversal "point" was present. In three
animals the probe was more or less perpendicular to layer II. In these
rats, phase reversal of gamma activity occurred within 100-200 µm
(Fig. 3). In the fifth rat, the probe did not penetrate into layer I,
and no reversal of theta or gamma phase was observed (see histology in
Fig. 5). Spectral analysis of gamma waves along the layer IV-layer I
axis of the entorhinal cortex revealed coherence values ranging from 0.2 to 0.5 (Fig. 2).
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Figure 2.
Depth versus amplitude profiles of theta and gamma
oscillations in the entorhinal cortex. A, B, Averaged
extracellular field potentials illustrating theta and gamma
oscillations across layers I-III of the entorhinal cortex. The
averager was triggered by the positive peaks of filtered (1-20 Hz;
50-150 Hz) waves recorded from site 1 (bottom trace).
The wide null zone of gamma waves is attributable to the oblique
penetration of the recording silicon probe (shown in Fig. 1).
C, Corresponding current source density analysis of
gamma oscillation. Cold colors; Sinks; hot
colors, sources. D-G, Laminar distribution of
power, coherence, and phases of theta and gamma oscillations. Coherence
and phase measurements are relative to site 2 from
bottom. The values indicate summed values from the
spectra from 6 to 12 Hz (theta) and 40 to 120 Hz (gamma). Note phase
reversal of gamma oscillation between layers I and II.
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Figure 3.
Relation of entorhinal theta to entorhinal gamma.
A, Single sweep illustrating theta and gamma waves in
the entorhinal cortex at six recording positions along the axis of a
16-site recording probe. Six black traces are
gamma-filtered (50-150 Hz); two gray traces show
concurrent theta waves (1-20 Hz). Numerals at
right refer to recording positions on silicon probe.
Theta records at positions 1 (layer I) and
8 (layer III) are from same sites as gamma traces shown.
Note amplitude variation of gamma oscillation at different recording
sites. Note also the prominent relation between phase of theta and the
amplitude gamma waves. B, Averaged (n = 402) extracellular field potentials (wide
band) as triggered from negative peaks of local gamma oscillation (at
site 3). Note the sudden phase reversal of gamma waves
between sites 1 and 2. C,
arrow, Recording site 1; asterisk, tissue
tear.
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We also examined the relationship between gamma waves at layer II-III
sites and gamma activity at ipsilateral dentate-hilar sites
(n = 8). Figure 4
illustrates prominent synchrony of gamma patterns between a site in the
lateral entorhinal cortex and the dorsal hippocampus. Note the multiple
peaks and troughs in the cross-correlogram. This example represents the
highest coherence observed between any two sites in the entorhinal
cortex and hippocampus. Although all sites showed synchrony in the
theta range, this varied considerably for gamma.
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Figure 4.
Synchrony between theta and gamma oscillations
recorded within layers I-III of caudalateral entorhinal cortex and
ipsilateral dentate region. A, Averaged field potentials
(n = 366) from the dentate hilar region
(gray traces) and layer III of EC (black trace), triggered by negative peaks of dentate gamma
oscillation (short trace; filtered 50-150 Hz).
B, Averaged field potentials (n = 262) from EC layers III and I (black traces) and
ipsilateral dentate hilus (gray trace) triggered
by negative peaks (layer III) of entorhinal gamma oscillation
(short trace; filtered 50-150 Hz). C,
Cross-correlogram between entorhinal gamma waves and dentate gamma
oscillation. The 0 (reference) point was the negative
peak of filtered layer III gamma waves. Arrows point to
multiple peaks in cross-correlogram, emphasizing the transient
synchronicity in the entorhinal and hippocampal oscillators.
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Superficial layer neurons discharge in relation to local theta and
gamma oscillations
We analyzed the discharge characteristics of 31 putative single
neurons (as defined by refractory periods of >1.0 msec) and multiunit
activity (spikes >100 µV but with refractory periods of <1.0 msec)
at 53 sites within layers I-III of the entorhinal cortex
(n = 45 penetrations), as well as in the superficial
layers of the presubiculum (n = 8) in 19 rats. The
majority of single neurons (27 of 31) and multiunit activity (47 of 53)
exhibited a peak in the cross-correlogram near the zero reference (±5
msec) point of the local gamma oscillation. All single-unit and
multiunit activity in layer II-III was correlated to local field theta
waves.
The majority of single neurons fired very slowly (<5 Hz), often
exhibiting sustained periods (tens of seconds) of quiescence, although
occasionally emitting one to four spikes (typically one) on a sequence
of theta cycles. These neurons exhibited varying degrees of modulation
for multiple cycles of the gamma oscillation. Typically, putative
single neurons exhibited a single prominent peak near the zero
reference, minimal firing in the adjacent troughs, and one or two
additional broader peaks (Fig. 5). The
broadness of the nonzero peaks may result from several factors,
including (1) rapid changes in the frequency of the oscillation as it
develops and degenerates and (2) the fact that the local field event
reflects summation of synaptic potentials over a limited, but
ill-defined, area of space. Both of these factors place limitations on
detecting and defining the peak of the local field potential, which
might reflect synaptic input that contributed to the discharge of any given neuron (for discussion, also see Laurent et al., 1996). One
should note that the local field oscillation reflects summation of
synaptic input that is constantly varying in time, amplitude, and
location. Figure 3 illustrates the amplitude and spatial variation of
the local gamma oscillation in filtered traces.
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Figure 5.
Neuronal activity in layers II and III is
phase-locked to gamma waves. A, Adjacent Nissl-stained
sections illustrating tip of electrode near layer II of the entorhinal
cortex taken from brain pictured at B. B,
Silicon probe as it emerges from sectioned rat brain during
histological processing. Inset, Probe in relation to
edge of brain (arrows are placed at ventral brain
surface). No reversal of gamma oscillation was observed along any of 16 dorsoventral sites along this probe, which recorded from layers II-V
of the entorhinal cortex. C, Relationship between
simultaneously recorded single units and local gamma oscillation,
recorded with the lower eight recording sites of the silicon probe in
layers II and III. Arrows point to two single units
(verified by the absence of spikes 1 msec in autocorrelograms); a
third single unit from site number 15 was also recorded, which did not
discharge in trace shown. Top trace (from site 13),
Single 50 msec gamma wave epoch (50-150 Hz). Traces
9-16, Unit filtered traces (0.5-5 KHz). Note prominent single
units during this 50 msec sweep in traces 11 and
13, as well as their phase relationship to gamma field
oscillation. D, Cross-correlograms between units
11, 13, and 15 (not
present in trace shown in C) and gamma field
oscillation. Note discharge peaks of units in relation to average gamma
wave (top trace). Traces at
right of each correlogram illustrate unfiltered (wide-band) average of first 30 discriminated waveforms
(top) and last 30 discriminated waveforms
(bottom).
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Most neurons exhibited very slow firing rates and discharged
irregularly. Figure 5 illustrates the relation of putative single-unit discharges in a single sweep. The unit shown in electrode position 11, for which a cumulative cross-correlogram is also shown (Fig. 5D), discharged a single spike during this epoch, as did the
unit shown in position 13. Over a 90 sec REM sleep episode, unit 13 discharged at a rate of 3.9 spikes/sec compared with 0.46 spikes/sec for unit 11. These observations illustrate the low probability of
concurrent discharge among pairs of layer II-III neurons. Yet, the
temporal occurrence of spike discharge in the vast majority of layer
II-III neurons was phase-locked to the slow (~125 msec) theta waves
and to the associated fast (~10-25 msec) gamma cycles (Fig. 5).
These observations indicated that spatially distinct, slowly
discharging cells can nevertheless maintain a population oscillation
and provide a gamma frequency net excitation to their hippocampal
targets. Slowly discharging cells had a relatively wide action
potential (>0.6 msec at the base, unfiltered).
Two of 31 single neurons were characterized as fast-spiking cells,
emitting sustained firing >20 Hz for long periods (minutes). These two
neurons had short-duration action potentials (<0.5 msec, unfiltered).
They were strongly theta-modulated and emitted trains of 2-10 action
potentials on each theta cycle with quiescence between cycles or
exhibiting a relatively sustained firing with their frequency waxing
and waning by the phase changes of the local theta cycle (Fig.
6). The discharge of both neurons was phase-related to the local gamma field during both exploratory locomotion and REM sleep. In addition, they were also modulated by the
lower-amplitude gamma oscillations present during immobility and
slow-wave sleep. Both neurons were located within layer II. On the
basis of their distinct physiological features, we tentatively suggest
that these fast-firing cells correspond to aspiny stellate interneurons
of layer II.
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Figure 6.
Relationship of putative interneuron of layer II
to local theta and gamma oscillations. A1, A2, Two 400 msec sweeps from single recording electrode in layer II of the
entorhinal cortex. Top trace is filtered for unit
activity (0.5-5 KHz), middle for gamma oscillation
(50-150 Hz), and lower gray trace for theta (1-20 Hz).
Note rhythmic trains of firing in A1 in association with nested theta-gamma cycles, as well as a more continous discharge pattern in A2. B, Relationship of
single-unit activity to local field gamma oscillation. Top gray
trace, Average wide-band trace (1 Hz-5 kHz), triggered from
negative peak of local gamma oscillation (n = 244).
Bottom, Cross-correlogram showing prominent theta-gamma modulation of unit discharge. Inset at
right, Autocorrelogram of this unit.
Inset, Unfiltered (1 Hz-5 kHz) average of first 30 discriminated waveforms (top) and last 30 discriminated
waveforms (bottom). Note short duration (<0.5 msec) of
the action potential.
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DISCUSSION |
During theta waves, associated with exploratory locomotion and REM
sleep (Green and Arduini, 1954; Grastyán et al., 1959; Vanderwolf, 1969), neurons within the entorhinal-hippocampal input network discharge in an organized manner (Mitchell and Ranck, 1980;
Alonso and Garcia-Austt, 1987a,b; Stewart et al., 1992). Hippocampal
and entorhinal neurons are brought together such that they discharge in
discrete time windows within the 50-100 msec time frames of a theta
wave. The present findings reveal much greater temporal precision in
the discharge of layer II-III neurons. Individual layer II-III
neurons discharged at a very low rate (<5 Hz), but in phase with local
gamma oscillations that occur nested within the theta cycle. Thus,
subsets of entorhinal neurons discharge together in 10-25 msec time
frames, with varying subsets discharging every 50-100 msec.
The present findings demonstrate that during theta activity a
distributed population output, entrained into local gamma rhythms, is
fed into the circuitry of the hippocampus. Concurrently, the theta-generating mechanism within the hippocampus brings about a
dynamic gamma frequency modulation of hippocampal neurons (Bragin et
al., 1995). Previous studies have demonstrated that gamma oscillations in the dentate-hilar region virtually disappear after surgical removal
of the entorhinal cortex (Bragin et al., 1995; Charpak et al.,
1995).
It is important to recognize that theta-gamma dynamics are not
developing equally throughout the entire spatial extent of the network,
nor necessarily at fixed frequencies. Rather, transiently synchronized
neuronal discharges are emerging within varying topographical locations, involving varying subpopulations of neurons and at a rapidly
evolving (but biologically constrained) range of frequencies (Traub et
al., 1996; Wang and Buzsáki, 1996). Two issues concerning this
variability need to be addressed by subsequent studies. The first issue
concerns the variability in the gamma frequency (40-100 Hz). Previous
findings concerning the theta-gamma relationship in the dentate-hilar
region demonstrate that in this region, gamma frequency varies as a
function of theta frequency (Bragin et al., 1995). The results of the
present experiments suggest a similar relationship between theta and
gamma oscillations in the entorhinal cortex.
The second issue concerns the synchronization of dentate-hilar gamma
and entorhinal gamma. In all cases we observed synchronization of gamma
oscillations in the theta range (50-100 msec) between sites in the
dentate-hilar region and the entorhinal cortex. Synchronization in the
gamma frequency varied considerably, although we observed cases in
which multiple peaks in the cross-correlogram were evident. In the
animal with the most synchronized relationship between any two sites,
the electrodes were located in the caudal-lateral aspect of the
entorhinal cortex and in the dorsal dentate-hilar region. At least
part of the interanimal variability may be accounted for by the
specific topographical profile of entorhinal-hippocampal interconnections. Recent findings suggest that there is greater specificity in the anatomical organization of the perforant path input
than appreciated previously, with three relatively segregated topographical bands oriented rostrocaudally, innervating three segregated septotemporal domains of the dentate gyrus (D. G. Amaral and C. Dolorfo, personal communication) and fairly circumscribed patches in the CA1 region (Tamamaki and Nojyo, 1995). We suggest that
synchrony should vary systematically depending on topographical connectivity, and a systematic mapping of the "physiological
connectivity" of this projection, based on a more precise mapping of
the anatomical connectivity, warrants further investigation. We predict
that synchronization in the gamma frequency range will be a constant feature of the relationship between entorhinal gamma and dentate-hilar gamma, when electrodes are positioned into interconnected domains of
the entorhinal-hippocampal axis.
Potential mechanisms
We have demonstrated that gamma oscillations are a feature of the
micro-EEG observed in the superficial layers of the entorhinal cortex
during theta. Furthermore, the discharge of layer II-III neurons is
entrained into a population dynamic in association with the gamma
frequency oscillation. How could this dynamic be achieved by local
macrocircuits? Within the hippocampus, GABAergic interneurons can
produce rhythmic, population discharges in the gamma frequency range.
This output then imposes a hyperpolarizing oscillation on the membrane
potential of principal neurons (Buzsáki et al., 1983;
Soltész and Deschénes, 1993; Bragin et al., 1995; Whittington et al., 1995). The dentate-hilar gamma oscillations thus
reflect synchronous membrane oscillations in pyramidal and stellate
neurons caused by rhythmic IPSPs (Buzsáki and Chrobak, 1995; Sik
et al., 1995; Whittington et al., 1995; Acsády et al., 1996;
Freund and Buzsáki, 1996; Gulyás et al., 1996; Traub et al., 1996; Wang and Buzsáki, 1996). Alternatively, recent
findings suggest that a specific subclass of cortical pyramidal
neurons, "chattering cells," can intrinsically generate gamma
frequency discharges on suprathreshold depolarization (Gray and
McCormick, 1996). These putative excitatory neurons, observed in layer
II-III of both striate and prestriate cortex, could contribute to the generation of gamma band oscillations in those regions. The presence of
chattering pyramidal neurons in the entorhinal cortex, however, has yet
to be demonstrated.
Inhibition of superficial layer entorhinal cortical neurons, even in
the presence of powerful excitatory input, is a consistent feature of
this region of cortex (Finch et al., 1986, 1988; Jones and Heinemann;
1988; Jones, 1993; Jones and Buhl, 1993; Chrobak and Buzsáki,
1994). Jones and Buhl (1993) observed a very small percentage of
(presumably GABAergic) cells in layer II that were fast spiking (up to
200 Hz) and that extensively arborized in layer II, forming basket-like
complexes. A single cell with comparable properties has been described
in vivo (Tamamaki and Nojyo, 1995). Based on detailed
morphological and anatomical analysis of parvalbumin-immunoreactive interneurons in the entorhinal cortex, Wouterlood and colleagues (1995)
suggested that the strong inhibitory influence on layer II cells (Jones
and Buhl, 1993) was mediated by parvalbumin-positive basket cells. By
innervating the perisomatic region of layers II and III, these
interneurons would be in a position to generate the synaptic currents
observed in the present study. Studies combining in vivo
intracellular recording and extracellular field recordings would be a
powerful means of determining the physiological properties of
individual pyramidal neurons and interneurons in the entorhinal cortex,
as well as the role of individual neuronal populations to the
generation of gamma frequency oscillations.
Possible role of synchrony in neuronal communication and
synaptic efficacy
Bringing sparsely firing neurons within the entorhinal cortex
together on such a short time scale may provide the requisite means for
entorhinal neurons to initiate neuronal discharge at hippocampal
targets. A class of fast-spiking interneurons within the dentate gyrus
and CA1-CA3 regions as well as other cortical regions is the first to
discharge in response to afferent activation and to respond
repetitively (Buzsáki and Eidelberg, 1982; Buzsáki, 1984;
Llinás et al., 1991; Gulyas et al., 1993). During theta, hippocampal interneurons are entrained into gamma frequency volleys that periodically hyperpolarize the dendritic and somatic compartments of their target cells (Penttonen et al., 1997). The present findings demonstrate that the entorhinal input is entrained into cooperative oscillatory volleys at the same frequency as the rhythmic
hyperpolarization of their hippocampal targets (Bragin et al., 1995).
Synchronized excitatory inputs that arrive at the right phase of the
rhythmic membrane oscillations may then be able to discharge principal cell targets. Conversely, excitatory potentials arriving out of phase
will be less efficient because of the shunting and hyperpolarizing effects of inhibitory potentials at the soma.
The temporal dynamics underlying resonant entrainment of hippocampal
neurons may be critically related to the in vivo production of synaptic long-term potentiation (LTP) and long-term depression (LTD)
(Larson and Lynch, 1986; Rose and Dunwiddie, 1986; Berger and Yeckel,
1991; Huerta and Lisman, 1996). Cooperative activity in the afferent
input is a requisite for both LTP and LTD (McNaughton et al., 1978;
Bliss and Collingridge, 1993). Huerta and Lisman (1996) have
demonstrated the relationship between the phase of population
oscillation in the theta range and LTP/LTD (Huerta and Lisman, 1996).
The gamma frequency synchronization of the entorhinal output would
appear to place faster temporal constraints on the activation and
inactivation of membrane currents critical to LTP/LTD.
Conclusions
Gamma frequency synchronization of neuronal activity occurs in
virtually all forebrain structures of the mammalian brain. This
population pattern is likely to reflect a fundamental operational mode
of cortical networks. Synchronization of neuronal populations is often
revealed by field oscillations (Gray and Singer, 1989; Bragin et al.,
1995; Chrobak and Buzsáki, 1996a; Steriade et al., 1996). The
theta-gamma phase locking of principal cells that develop within the
entorhinal cortex and hippocampus may provide a basis for effective
communication among these neuronal populations.
| |
FOOTNOTES |
Received Oct. 15, 1996; revised Oct. 3, 1997; accepted Oct. 9, 1997.
This work was supported by the Alzheimer's Association, National
Institutes of Health Grants NS34994 and 1P41RR09754, Human Frontier
Science Program, and Whitehall Foundation. We thank Heather Read and
Anatol Bragin for all their help, comments, and discussion, as well as
Kensall Wise and Jamille Hetke for supplying silicon probes.
Correspondence should be addressed to Gyorgy Buzsáki, Center for
Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ 07102.
Dr. Chrobak's present address: Center for Neuroscience, University of
California-Davis, 1544 Newton Court, Davis, CA 95616.
| |
REFERENCES |
-
Acsády L,
Görcs TJ,
Freund TF
(1996)
Different populations of VIP-immunoreactive interneurons are specialized to control pyramidal cells or interneurons in the hippocampus.
Neuroscience
73:317-334[Web of Science][Medline].
-
Alonso A,
Garcia-Austt E
(1987a)
Neuronal sources of theta rhythm in the entorhinal cortex of hte rat. I. Laminar distribution of theta field potentials.
Exp Brain Res
67:493-501[Web of Science][Medline].
-
Alonso A,
Garcia-Austt E
(1987b)
Neuronal sources of theta rhythm in the entorhinal cortex of the rat. II. Phase relations between unit discharges and theta field potentials.
Exp Brain Res
67:502-509[Web of Science][Medline].
-
Amaral DG,
Witter MP
(1995)
Hippocampal formation.
In: The rat nervous system, Ed 2 (Paxinos G,
ed), pp 443-493. San Diego: Academic.
-
Berger TW,
Yeckel MF
(1991)
Long-term potentiation of entorhinal afferents to the hippocampus: enhanced propagation of activity through the trisynaptic pathway.
In: Long-term potentiation: from biophysics to behavior (Baudry M,
Davis JL,
eds), pp 327-356. Cambridge, MA: MIT.
-
Bliss TVP,
Collinridge GL
(1993)
A synaptic model of memory: long-term potentiation in the hippocampus.
Nature
361:31-39[Medline].
-
Braak H,
Braak E
(1995)
Staging of Alzheimer's disease-related neurofibrillary changes.
Neurobiol Aging
16:271-284[Web of Science][Medline].
-
Bragin A,
Jandó G,
Nadasdy Z,
Hetke J,
Wise K,
Buzsáki G
(1995)
Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat.
J Neurosci
15:47-60[Abstract].
-
Buzsáki G
(1984)
Feed-forward inhibition in the hippocampal formation.
Prog Neurobiol
22:131-153[Web of Science][Medline].
-
Buzsáki G
(1989)
Two-stage model of memory trace formation: a role for "noisy" brain states.
Neuroscience
31:551-570[Web of Science][Medline].
-
Buzsáki G,
Eidelberg E
(1982)
Direct afferent excitation and long-term potentiation of hippocampal interneurons.
J Neurophysiol
48:597-607[Free Full Text].
-
Buzsáki G,
Chrobak JJ
(1995)
Temporal structure in spatially organized neuronal ensembles: a role for interneuron networks.
Curr Opin Neurobiol
5:504-510[Web of Science][Medline].
-
Buzsáki G,
Leung LS,
Vanderwolf CH
(1983)
Cellular basis of hippocampal EEG in the behaving rat.
Brain Res
6:139-171[Web of Science].
-
Buzsáki G,
Horváth Z,
Urioste R,
Hetke J,
Wise K
(1992)
High-frequency network oscillation in the hippocampus.
Science
256:1025-1027[Abstract/Free Full Text].
-
Charpak S,
Paré D,
Llinás R
(1995)
The entorhinal cortex entrains fast CA1 hippocampal oscillations in the anaesthetized guinea-pig: role of the monosynaptic component of the perforant path.
Eur J Neurosci
7:1548-1557[Web of Science][Medline].
-
Chrobak JJ,
Buzsáki G
(1994)
Selective activation of deep layer (V-VI) retrohippocampal cortical neurons during hippocampal sharp waves in the behaving rat.
J Neurosci
14:6160-6170[Abstract].
-
Chrobak JJ,
Buzsáki G
(1996a)
High-frequency oscillations in the output networks of the hippocampal-entorhinal axis of the freely-behaving rat.
J Neurosci
16:3056-3066[Abstract/Free Full Text].
-
Chrobak JJ,
Buzsáki G
(1996b)
Entorhinal-hippocampal network dynamics constrain synaptic potentiation and memory formation.
In: Long-term potentiation: current issues (Baudry M,
Davies JL,
eds), pp 215-232. Cambridge, MA: MIT.
-
Finch DM,
Wong EE,
Derian EL,
Babb TL
(1986)
Neurophysiology of limbic system pathways in the rat: projections from the subicular complex and hippocampus to the entorhinal cortex.
Brain Res
397:205-213[Web of Science][Medline].
-
Finch DM,
Tan AM,
Isokawa-Akesson M
(1988)
Feedforward inhibition of the rat entorhinal cortex and subicular complex.
J Neurosci
8:2213-2226[Abstract].
-
Freeman W,
Barrie F
(1994)
Chaotic oscillations and the genesis of meaning in the cerebral cortex.
In: Temporal coding in the brain (Buzsáki G,
Llinás R,
Singer W,
Berthoz A,
Christian Y,
eds). Berlin: Springer.
-
Fregnac Y
(1994)
Oscillatory neuronal activity in visual cortex: a critical re-evaluation.
In: Temporal coding in the brain (Buzsáki G,
Llinás R,
Singer W,
Berthoz A,
Christian Y,
eds), pp 81-102. Berlin: Springer.
-
Freund TF,
Buzsáki G
(1996)
Interneurons of the hippocampus.
Hippocampus
6:347-470[Web of Science][Medline].
-
Gallyas F,
Guldner FH,
Zoltay G,
Wolff JR
(1990)
Golgi-like demonstration of "dark" neurons with an argyrophil III method for experimental neuropathology.
Acta Neuropathol (Berl)
79:620-628[Medline].
-
Grastyán E,
Lissak K,
Madarasz I,
Donhoffer H
(1959)
The hippocampal electrical activity during the development of conditioned reflexes.
Electroencephalogr Clin Neurophysiol
11:409-430[Web of Science][Medline].
-
Gray CM
(1994)
Synchronous oscillations in neuronal systems: mechanisms and functions.
Comput Neurosci
1:11-38.
-
Gray CM,
Singer W
(1989)
Stimulus-specific oscillations in orientation columns of cat visual cortex.
Proc Natl Acad Sci USA
86:1698-1702[Abstract/Free Full Text].
-
Gray CM,
McCormick DA
(1996)
Chattering cells: superficial pyramidal neurons contributing to the generation of synchronous oscillations in the visual cortex.
Science
274:109-113[Abstract/Free Full Text].
-
Green JD,
Arduini AA
(1954)
Hippocampal electrical activity in arousal.
J Neurophysiol
17:533-557[Free Full Text].
-
Gulyas AI,
Miles R,
Hajos N,
Freund TF
(1993)
Precision and variability in postsynaptic target selection of inhibitory cells in the hippocampal CA3 region.
Eur J Neurosci
5:1729-1751[Web of Science][Medline].
-
Gulyás AI,
Hájos N,
Freund TF
(1996)
Interneurons containing calretinin are specialized to control other interneurons in the rat hippocampus.
J Neurosci
16:3397-3411[Abstract/Free Full Text].
-
Hebb DO
(1949)
In: The organization of behavior. New York: Wiley.
-
Heurta PT,
Lisman JE
(1996)
Bidirectional synaptic plasticity induced by a single burst during cholinergic theta oscillation in CA1 in vitro.
Neuron
15:1053-1063.
-
Hyman BT,
Van Hoesen GW,
Damasio AR,
Barnes CL
(1984)
Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.
Science
225:1168-1170[Abstract/Free Full Text].
-
Jones RSG
(1993)
Entorhinal-hippocampal connections: a speculative view of their function.
Trends Neurosci
16:58-64[Web of Science][Medline].
-
Jones RSG,
Buhl EH
(1993)
Basket-like interneurones in layer II of the entorhinal cortex exhibit a powerful NMDA-mediated synaptic excitation.
Neuroscience
149:35-39.
-
Jones RSG,
Heinemann U
(1988)
Synaptic and intrinsic responses of medial entorhinal cortical cells in normal and magnesium-free medium in vitro.
J Neurophysiol
59:1476-1496[Abstract/Free Full Text].
-
Larson J,
Lynch G
(1986)
Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events.
Science
232:985-988[Abstract/Free Full Text].
-
Laurent G
(1996)
Dynamical representations of odors by oscillating and evolving neural assemblies.
Trends Neurosci
19:489-496[Web of Science][Medline].
-
Laurent G,
Wehr M,
Davidowitz H
(1996)
Temporal representations of odors in an olfactory network.
J Neurosci
16:3837-3847[Abstract/Free Full Text].
-
Leung LW,
Buzsáki G
(1983)
Spectral analysis of hippocampal unit train in relation to hippocampal EEG.
Electroencephalogr Clin Neurophysiol
56:668-671[Web of Science][Medline].
-
Llinás RR
(1988)
The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function.
Science
242:11654-11664.
-
Llinás R,
Grace AA,
Yarom Y
(1991)
In vitro neurons in mammalian cortical layer 4 exhibit intrinsic oscillatory activity in the 10- to 50 Hz frequency range.
Proc Natl Acad Sci USA
88:897-901[Abstract/Free Full Text].
-
McNaughton BL,
Douglas RM,
Goddard GV
(1978)
Synaptic enhancement in fascia dentata: cooperativity among coactive afferents.
Brain Res
157:277-193[Web of Science][Medline].
-
Mitchell SJ,
Ranck JB
(1980)
Generation of theta rhythm in medial entorhinal cortex of freely moving rats.
Brain Res
189:49-66[Web of Science][Medline].
-
Murthy VN,
Fetz EE
(1992)
Coherent 25- to 35- Hz oscillations in the sensorimotor cortex of awake behaving monkeys.
Proc Natl Acad Sci USA
89:5670-5674[Abstract/Free Full Text].
-
Pavlides C,
Greenstein YJ,
Grudman M,
Winson J
(1988)
Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta rhythm.
Brain Res
439:383-387[Web of Science][Medline].
-
Paxinos G,
Watson C
(1986)
In: The rat brain in stereotaxic coordinates, Ed 2. New York: Academic.
-
Penttonen M, Kamondi A, Acsády L, Buzsáki
G (1997) Intracellular correlates of hippocampal gamma
oscillation in vivo. Soc Neurosci Abstr, in press.
-
Rose GM,
Dunwiddie TV
(1986)
Induction of hippocampal long-term potentiation using physiologically patterned stimulation.
Neurosci Lett
69:244-248[Web of Science][Medline].
-
Sik A,
Penttonen M,
Ylinen A,
Buzsáki G
(1995)
Hippocampal CA1 interneurons: an in vivo intracellular labeling study.
J Neurosci
15:6651-6665[Abstract/Free Full Text].
-
Singer W
(1993)
Synchronization of cortical activity and its putative role in information processing and learning.
Annu Rev Physiol
55:349-374[Web of Science][Medline].
-
Soltész I,
Deschénes M
(1993)
Low- and high-frequency membrane potential oscillations during theta activity in CA1 and CA3 pyramidal neurons of the rat hippocampus under ketamine-xylazine anesthesia.
J Neurophysiol
70:97-116[Abstract/Free Full Text].
-
Steriade M,
Amzica F
(1996)
Intracortical and corticothalamic coherency of fast spontaneous oscillations.
Proc Natl Acad Sci USA
93:2533-2538[Abstract/Free Full Text].
-
Steriade M,
Gloor P,
Llinás RR,
Lopes da Silva FH,
Mesulam M-M
(1990)
Basic mechanisms of cerebral rhythmic activities.
Electroencephalogr Clin Neurophysiol
76:481-508[Web of Science][Medline].
-
Steriade M,
McCormick DA,
Sejnowski TJ
(1993)
The sleeping and aroused brain: thalamocortical oscillations in neurons and networks.
Nature
262:679-685.
-
Steriade M,
Amzica F,
Contreras D
(1996)
Synchronization of fast (30-40 Hz) spontaneous cortical rhythms during brain activation.
J Neurosci
16:392-417[Abstract/Free Full Text].
-
Steward O,
Scoville SA
(1976)
Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat.
J Comp Neurol
169:347-370[Web of Science][Medline].
-
Stewart M,
Quirk GJ,
Barry M,
Fox SE
(1992)
Firing relation of medial entorhinal neurons to the hippocampal theta rhythm in urethane anesthetized and walking rats.
Exp Brain Res
90:21-28[Web of Science][Medline].
-
Tamamaki N,
Nojyo Y
(1995)
Preservation of topography in the connections between the subiculum, field CA1 and the entorhinal cortex in the rats.
J Comp Neurol
353:379-390[Web of Science][Medline].
-
Traub RD,
Whittington MA,
Colling SB,
Buzsáki G,
Jefferys JGR
(1996)
Analysis of gamma rhythms in the rat hippocampus in vitro and in vivo.
J Physiol (Lond)
493:471-484[Abstract/Free Full Text].
-
Vanderwolf CH
(1969)
Hippocampal electrical activity and voluntary movement in the rat.
Electroencephalogr Clin Neurophysiol
26:407-418[Web of Science][Medline].
-
Van Hoesen GW,
Hyman BT,
Damasio AR
(1991)
Entorhinal cortex pathology in Alzheimer's disease.
Hippocampus
1:1-8[Medline].
-
Wang X-J,
Buzsáki G
(1996)
Gamma oscillation by synaptic inhibition in an interneuronal network model.
J Neurosci
16:6402-6413[Abstract/Free Full Text].
-
Whittington MA,
Traub RD,
Jefferys JGR
(1995)
Metabotropic receptor activation drive synchronized 40 Hz oscillations in networks of inhibitory interneurons.
Nature
373:612-615[Medline].
-
Wise KD,
Najafi K
(1991)
Microfabrication techniques for integrated sensors and microsystems.
Science
254:1335-1342[Abstract/Free Full Text].
-
Witter MP,
Groenewegen HJ
(1984)
Laminar origin and septotemporal distribution of entorhinal and perirhinal projections to the hippocampus in the cat.
J Comp Neurol
224:371-385[Web of Science][Medline].
-
Wouterlood FG,
Hartig W,
Bruckner G,
Witter MP
(1995)
Paravalbumin-immunoreactive neurons in the entorhinal cortex of the rat: localization, morphology, connectivity and ultrastructure.
J Neurocytol
24:135-153[Web of Science][Medline].
-
Ylinen A,
Sik A,
Bragin A,
Nadásdy Z,
Jandó G,
Szabó I,
Buzsáki G
(1995)
Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms.
J Neurosci
15:30-46[Abstract].
Copyright © 1998 Society for Neuroscience 0270-6474/98/181388-11$05.00/0
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3209 - 3219.
[Abstract]
[Full Text]
[PDF]
|
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|
|
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C. W. Ang, G. C. Carlson, and D. A. Coulter
Massive and Specific Dysregulation of Direct Cortical Input to the Hippocampus in Temporal Lobe Epilepsy.
J. Neurosci.,
November 15, 2006;
26(46):
11850 - 11856.
[Abstract]
[Full Text]
[PDF]
|
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|
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I. van Welie, M. W. H. Remme, J. A. van Hooft, and W. J. Wadman
Different levels of Ih determine distinct temporal integration in bursting and regular-spiking neurons in rat subiculum
J. Physiol.,
October 1, 2006;
576(1):
203 - 214.
[Abstract]
[Full Text]
[PDF]
|
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R. T. Canolty, E. Edwards, S. S. Dalal, M. Soltani, S. S. Nagarajan, H. E. Kirsch, M. S. Berger, N. M. Barbaro, and R. T. Knight
High gamma power is phase-locked to theta oscillations in human neocortex.
Science,
September 15, 2006;
313(5793):
1626 - 1628.
[Abstract]
[Full Text]
[PDF]
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E. Labyt, L. Uva, M. de Curtis, and F. Wendling
Realistic Modeling of Entorhinal Cortex Field Potentials and Interpretation of Epileptic Activity in the Guinea Pig Isolated Brain Preparation
J Neurophysiol,
July 1, 2006;
96(1):
363 - 377.
[Abstract]
[Full Text]
[PDF]
|
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M. O. Cunningham, J. Hunt, S. Middleton, F. E. N. LeBeau, M. G. Gillies, C. H. Davies, P. R. Maycox, M. A. Whittington, and C. Racca
Region-specific reduction in entorhinal gamma oscillations and parvalbumin-immunoreactive neurons in animal models of psychiatric illness.
J. Neurosci.,
March 8, 2006;
26(10):
2767 - 2776.
[Abstract]
[Full Text]
[PDF]
|
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|
|
|
|
C. W. Ang, G. C. Carlson, and D. A. Coulter
Hippocampal CA1 Circuitry Dynamically Gates Direct Cortical Inputs Preferentially at Theta Frequencies
J. Neurosci.,
October 19, 2005;
25(42):
9567 - 9580.
[Abstract]
[Full Text]
[PDF]
|
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|
|
|
|
P. Lakatos, A. S. Shah, K. H. Knuth, I. Ulbert, G. Karmos, and C. E. Schroeder
An Oscillatory Hierarchy Controlling Neuronal Excitability and Stimulus Processing in the Auditory Cortex
J Neurophysiol,
September 1, 2005;
94(3):
1904 - 1911.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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C. Borgers, S. Epstein, and N. J. Kopell
Background gamma rhythmicity and attention in cortical local circuits: A computational study
PNAS,
May 10, 2005;
102(19):
7002 - 7007.
[Abstract]
[Full Text]
[PDF]
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|
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|
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J. M. Palva, S. Palva, and K. Kaila
Phase Synchrony among Neuronal Oscillations in the Human Cortex
J. Neurosci.,
April 13, 2005;
25(15):
3962 - 3972.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. I. Netoff, M. I. Banks, A. D. Dorval, C. D. Acker, J. S. Haas, N. Kopell, and J. A. White
Synchronization in Hybrid Neuronal Networks of the Hippocampal Formation
J Neurophysiol,
March 1, 2005;
93(3):
1197 - 1208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Traub, A. Bibbig, F. E. N. LeBeau, M. O. Cunningham, and M. A. Whittington
Persistent gamma oscillations in superficial layers of rat auditory neocortex: experiment and model
J. Physiol.,
January 1, 2005;
562(1):
3 - 8.
[Abstract]
[Full Text]
[PDF]
|
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|
|
|
|
N. Hajos, J. Palhalmi, E. O. Mann, B. Nemeth, O. Paulsen, and T. F. Freund
Spike Timing of Distinct Types of GABAergic Interneuron during Hippocampal Gamma Oscillations In Vitro
J. Neurosci.,
October 13, 2004;
24(41):
9127 - 9137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I Erchova, G Kreck, U Heinemann, and A. V. M Herz
Dynamics of rat entorhinal cortex layer II and III cells: characteristics of membrane potential resonance at rest predict oscillation properties near threshold
J. Physiol.,
October 1, 2004;
560(1):
89 - 110.
[Abstract]
[Full Text]
[PDF]
|
|
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|
|
|
|
S. J. Judge and M. E. Hasselmo
Theta Rhythmic Stimulation of Stratum Lacunosum-Moleculare in Rat Hippocampus Contributes to Associative LTP at a Phase Offset in Stratum Radiatum
J Neurophysiol,
September 1, 2004;
92(3):
1615 - 1624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Caruana and C. A. Chapman
Stimulation of the Parasubiculum Modulates Entorhinal Cortex Responses to Piriform Cortex Inputs In Vivo
J Neurophysiol,
August 1, 2004;
92(2):
1226 - 1235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Schreiber, I. Erchova, U. Heinemann, and A. V. M. Herz
Subthreshold Resonance Explains the Frequency-Dependent Integration of Periodic as Well as Random Stimuli in the Entorhinal Cortex
J Neurophysiol,
July 1, 2004;
92(1):
408 - 415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. O. Cunningham, C. H. Davies, E. H. Buhl, N. Kopell, and M. A. Whittington
Gamma Oscillations Induced by Kainate Receptor Activation in the Entorhinal Cortex In Vitro
J. Neurosci.,
October 29, 2003;
23(30):
9761 - 9769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. Dickson, G. Biella, and M. de Curtis
Slow Periodic Events and Their Transition to Gamma Oscillations in the Entorhinal Cortex of the Isolated Guinea Pig Brain
J Neurophysiol,
July 1, 2003;
90(1):
39 - 46.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Siegel and P. Konig
A Functional Gamma-Band Defined by Stimulus-Dependent Synchronization in Area 18 of Awake Behaving Cats
J. Neurosci.,
May 15, 2003;
23(10):
4251 - 4260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Mikkonen, T. Gronfors, J. J. Chrobak, and M. Penttonen
Hippocampus Retains the Periodicity of Gamma Stimulation In Vivo
J Neurophysiol,
November 1, 2002;
88(5):
2349 - 2354.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Baker, P. S. Pennefather, B. A. Orser, and F. K. Skinner
Disruption of Coherent Oscillations in Inhibitory Networks With Anesthetics: Role of GABAA Receptor Desensitization
J Neurophysiol,
November 1, 2002;
88(5):
2821 - 2833.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Oya, H. Kawasaki, M. A. Howard III, and R. Adolphs
Electrophysiological Responses in the Human Amygdala Discriminate Emotion Categories of Complex Visual Stimuli
J. Neurosci.,
November 1, 2002;
22(21):
9502 - 9512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Frank, U. T. Eden, V. Solo, M. A. Wilson, and E. N. Brown
Contrasting Patterns of Receptive Field Plasticity in the Hippocampus and the Entorhinal Cortex: An Adaptive Filtering Approach
J. Neurosci.,
May 1, 2002;
22(9):
3817 - 3830.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Frank, E. N. Brown, and M. A. Wilson
A Comparison of the Firing Properties of Putative Excitatory and Inhibitory Neurons From CA1 and the Entorhinal Cortex
J Neurophysiol,
October 1, 2001;
86(4):
2029 - 2040.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Shimono, F. Brucher, R. Granger, G. Lynch, and M. Taketani
Origins and Distribution of Cholinergically Induced beta Rhythms in Hippocampal Slices
J. Neurosci.,
November 15, 2000;
20(22):
8462 - 8473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. Dickson, G. Biella, and M. de Curtis
Evidence for Spatial Modules Mediated by Temporal Synchronization of Carbachol-Induced Gamma Rhythm in Medial Entorhinal Cortex
J. Neurosci.,
October 15, 2000;
20(20):
7846 - 7854.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Ji and J. A. Dani
Inhibition and Disinhibition of Pyramidal Neurons by Activation of Nicotinic Receptors on Hippocampal Interneurons
J Neurophysiol,
May 1, 2000;
83(5):
2682 - 2690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. V. Patterson, Y. Jin, M. Gierczak, W. P. Hetrick, S. Potkin, W. E. Bunney Jr, and C. A. Sandman
Effects of Temporal Variability on P50 and the Gating Ratio in Schizophrenia: A Frequency Domain Adaptive Filter Single-Trial Analysis
Arch Gen Psychiatry,
January 1, 2000;
57(1):
57 - 64.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Dvorak-Carbone and E. M. Schuman
Patterned Activity in Stratum Lacunosum Moleculare Inhibits CA1 Pyramidal Neuron Firing
J Neurophysiol,
December 1, 1999;
82(6):
3213 - 3222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. van der Linden, F. Panzica, and M. de Curtis
Carbachol Induces Fast Oscillations in the Medial but not in the Lateral Entorhinal Cortex of the Isolated Guinea Pig Brain
J Neurophysiol,
November 1, 1999;
82(5):
2441 - 2450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Kwon, B. F. O'Donnell, G. V. Wallenstein, R. W. Greene, Y. Hirayasu, P. G. Nestor, M. E. Hasselmo, G. F. Potts, M. E. Shenton, and R. W. McCarley
Gamma Frequency-Range Abnormalities to Auditory Stimulation in Schizophrenia
Arch Gen Psychiatry,
November 1, 1999;
56(11):
1001 - 1005.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Bracci, M. Vreugdenhil, S. P. Hack, and J. G. R. Jefferys
On the Synchronizing Mechanisms of Tetanically Induced Hippocampal Oscillations
J. Neurosci.,
September 15, 1999;
19(18):
8104 - 8113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. N. Ruskin, D. A. Bergstrom, and J. R. Walters
Multisecond Oscillations in Firing Rate in the Globus Pallidus: Synergistic Modulation by D1 and D2 Dopamine Receptors
J. Pharmacol. Exp. Ther.,
September 1, 1999;
290(3):
1493 - 1501.
[Abstract]
[Full Text]
|
|
|
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|
|
|
B. Kocsis, A. Bragin, and G. Buzsaki
Interdependence of Multiple Theta Generators in the Hippocampus: a Partial Coherence Analysis
J. Neurosci.,
July 15, 1999;
19(14):
6200 - 6212.
[Abstract]
[Full Text]
[PDF]
|
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D. N. Ruskin, D. A. Bergstrom, Y. Kaneoke, B. N. Patel, M. J. Twery, and J. R. Walters
Multisecond Oscillations in Firing Rate in the Basal Ganglia: Robust Modulation by Dopamine Receptor Activation and Anesthesia
J Neurophysiol,
May 1, 1999;
81(5):
2046 - 2055.
[Abstract]
[Full Text]
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Top
Abstract
Introduction
