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Volume 16, Number 17,
Issue of September 1, 1996
pp. 5547-5554
Copyright ©1996 Society for Neuroscience
Evidence for Differential Control of Posterior Hypothalamic,
Supramammillary, and Medial Mammillary Theta-Related Cellular Discharge
by Ascending and Descending Pathways
Ian J. Kirk,
Scott D. Oddie,
Jan Konopacki, and
Brian
H. Bland
Department of Psychology, Behavioral Neuroscience Research Group,
University of Calgary, Calgary, Alberta, Canada T2N 1N4
 ABSTRACT
- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- DISCUSSION
- FOOTNOTES
- REFERENCES
ABSTRACT 
Single-unit discharge was recorded from cells in the posterior
hypothalamic nucleus (PH), supramammillary nucleus (SuM), and medial
mammillary nucleus (MM) during hippocampal theta ( ) elicited by
stimulation of the reticular nucleus pontis oralis (RPO). In agreement
with previously published work, -related cells in the PH (12 cells)
were all classified as tonic -ON (increased tonic discharge rate
during hippocampal ), whereas those in the SuM (9 cells) and MM (15 cells) were all classified as phasic -ON (rhythmic discharge, in
phase with ongoing ). The effect of RPO stimulation on cell
discharge was tested after hippocampal was abolished by infusion of
procaine into the medial septum/vertical limb of the diagonal band. The
RPO-elicited discharge patterns of all PH tonic -ON cells and all
SuM phasic -ON cells survived septal procaine infusion. Further, the
discharge rate of PH cells and the frequency of burst discharge of SuM
cells during RPO stimulation both increased after the infusion. In
contrast, septal procaine infusion abolished the RPO-elicited rhythmic
discharge pattern in MM phasic -ON cells and attenuated their
discharge rates. These results indicate that the PH and SuM form parts
of an ascending system mediating hippocampal , whereas the MM
receives (and perhaps relays to other parts of the limbic system)
rhythmic input descending from the septo-hippocampal system. In
addition, PH and SuM receive descending inputs that limit the discharge
rates of their -related cells during hippocampal .
Key words:
intraseptal;
procaine;
hippocampal theta;
supramammillary
nucleus;
posterior hypothalamic nucleus;
medial mammillary nucleus;
rhythmic cell discharge
INTRODUCTION
Hippocampal theta () activity is a
large-amplitude, almost sinusoidal slow-wave activity, the occurrence
of which has been postulated to be involved in processes of hippocampal
synaptic plasticity (Pavlides et al., 1988 ; Buzsáki, 1989; Huerta
and Lisman, 1993) and related behavioral functions (O'Keefe and Nadel,
1978; Bland et al., 1986; Miller, 1991). There is evidence that may
be particularly important in hippocampal processing of spatial
information (O'Keefe and Recce, 1993; Skaggs and McNaughton, 1996). It
is well established that activation of an ascending system of
projections that have their putative origin in the nucleus reticularis
pontis oralis (RPO) elicits activity in the hippocampus (for
review, see Vertes, 1986). These ``synchronizing'' effects are
mediated via the medial septum/vertical limb of the diagonal band of
Broca (MS/vDBB) (for review, see Bland, 1986; Stewart and Fox, 1990).
However, there is a variety of recent evidence suggesting that, rather
than directly influencing MS/vDBB activity, as had been proposed
previously (O'Keefe and Nadel, 1978; Bland, 1986), reticular
influences are relayed to the MS/vDBB via a nuclei in the posterior
hypothalamic region.
Anatomical work has suggested that fibers from the RPO are relayed to
the MS/vDBB after first synapsing in the supramammillary nucleus (SuM)
(Veazy et al., 1982; Vertes, 1982, 1992; Vertes and Martin, 1988).
Procaine mapping of the system (Kirk and McNaughton, 1993) and rhythmic
multiunit (Kirk and McNaughton, 1991) and single unit (Bland et al.,
1993, 1995; Kirk et al., 1994; Kocsis and Vertes, 1994) activity in the
SuM during suggest that, in addition to acting as a relay, the SuM
transduces the intensity of RPO activity into the frequency of .
Lesions of, or procaine infused into the region of, the posterior
hypothalamus (PH) abolish hippocampal or septal activity (Kawamura
et al., 1961; Anchel and Lindsley, 1972; Robinson and Whishaw, 1974;
Bland et al., 1994, 1995; Oddie et al., 1994), and high-frequency (100 Hz) stimulation in the PH has been shown to be particularly effective
in eliciting hippocampal field activity (Bland and Vanderwolf,
1972) and pattern discharge in medial septal cells (Bland et al.,
1990). Thus, the PH has also been proposed to be a relay in the
ascending synchronizing system. Further, there are dense projections
from the posterior hypothalamic nucleus (PH) to the MS/vDBB (Vertes et
al., 1993a). In contrast to SuM, however, -related discharge in the
PH is tonic (Bland et al., 1995).
Neurons in the mammillary nuclei have also been shown to discharge
rhythmically at frequencies (Mignard et al., 1987; Kocsis and
Vertes, 1994; Bland et al., 1995), and repetitive bursts have been
recorded in vitro from the medial (MM) or lateral (LM)
mammillary nucleus (Alonso and Llinás, 1992; Llinás and
Alonso, 1992). As with hippocampal , this activity in the mammillary
nuclei may subserve their proposed role in memory in general (Mair et
al., 1979), and spatial memory in particular (Sziklas and Petrides,
1993). In contrast to the SuM and PH, however, it has been suggested
(although not unequivocally demonstrated) that the mammillary nuclei
may receive -frequency information descending from the
septo-hippocampal system (Alonso and Llinás, 1992; Llinás
and Alonso, 1992; Kocsis and Vertes, 1994). This information is likely
of hippocampal origin (Kocsis and Vertes, 1994) and may be relayed to
the mammillary bodies via the subiculum (Swanson and Cowan, 1975,
1977), i.e., via part of the circuit originally proposed by Papez
(1937).
In the current experiments, -related unit discharge was recorded
from PH, SuM, and MM during hippocampal elicited by RPO stimulation
(Vertes, 1982, 1986). Subsequently, hippocampal was abolished by
septal infusion of procaine. Thus, the contribution of -coded input
descending from the septo-hippocampal system (relative to input
ascending from the reticular formation) on the -related unit
discharge in the PH, SuM, and MM was determined.
MATERIALS AND METHODS
Thirty-four male Long-Evans rats (0.25-0.5 kg) were initially
anesthetized with a mixture of Halothane (M.T.C. Pharmaceuticals,
Cambridge, Ontario, Canada) in oxygen (~1.5% MAC) for jugular
cannula insertion. Halothane was subsequently discontinued, and
urethane (0.8 gm/ml) was administered via a jugular cannula as required
for the remaining surgical and experimental procedures. Rats were
secured in a stereotaxic apparatus, core temperature was maintained at
37°C, and heart rates were monitored constantly throughout the
experiments. Recording electrodes consisted of Kynar-insulated tungsten
(etched to 0.5-1.0 M tip resistance) for hippocampal field
activity, and glass electrodes (5.0-10 M) were filled with 0.5 M sodium acetate and 2% pontamine sky blue for unit
recording. Bipolar stimulating electrodes consisted of two insulated
stainless steel wires (250 µm) twisted together. Glass electrode tip
locations were marked by passing 50 µA of current for 10 min (5 min
cathodal, 5 min anodal). Procaine hydrochloride [20% (w/v) in saline,
2.0 µl, 0.5 µl/min] was infused into the MS/vDBB region by a
microinfusion pump via a 5 µl Hamilton syringe connected to a 30 gauge cannula by SILASTIC tubing (Dow Corning, Midland, MI).
Hippocampal recording electrodes were placed in the stratum moleculare
of the dentate gyrus (AP, Bregma  3.3 mm; L, midline 2.4 mm; DV, dura
2.5-3.0 mm). The tip of the infusion cannula was placed in the medial
septum (AP, Bregma +0.0 to 0.5 mm; L, midline 0.0 mm; DV, 5.0 to 6.0 mm). Glass unit recording electrodes were lowered through the PH/SuM/MM
region (AP, Bregma 3.0 to 5.0 mm; L, midline 0.0-0.2 mm DV, dura
7.0-9.5 mm) as described previously (Bland et al., 1995). Stimulating
electrodes were placed in the RPO (AP, Bregma 8.0 to 9.0 mm; L,
1.0-1.5 mm; DV, dura 8.0-9.0 mm). After perfusion and fixation of the
brain, frozen sections (40 µm) were taken serially, mounted on glass
slides, and stained with thionine for subsequent verification of
hippocampal field electrode and septal cannula placement and glass
electrode tip location.
Field and cell signals were stored on FM tape. Samples (20 sec) of cell
and field activity were taken during spontaneously occurring
large-amplitude irregular field activity (LIA), and subsequently during
4-5 Hz field activity elicited by 100 Hz (100-300 µA)
stimulation of the RPO. Sampling during RPO stimulation was from the
onset of stimulation. In contrast to higher frequencies of
stimulation-elicited (>6 Hz) (Bland and Vanderwolf, 1972),
intensities of RPO stimulation resulting in 4-5 Hz resulted in a
relatively stationary waveform over the 20 sec sample. Samples (20 sec
from stimulation onset) of field and cell activity were subsequently
taken during the same level of RPO stimulation after hippocampal was abolished by infusing procaine (2.0 µl) into the MS/vDBB region
(Brücke et al., 1959; Mizumori et al., 1989; Kirk and McNaughton,
1993; Lawson and Bland, 1993). Cell discharge (spontaneous and
stimulated every 2 min) was sampled until hippocampal recovered.
Data analysis and separation of cell discharge from stimulation
artifact was accomplished off-line using a PC microcomputer and a
software acquisition and analysis package (DataWave Technologies,
Longmount, CO). Unit cell activity was digitized through a 12 bit
analog-to-digital converter and sampled at a frequency of ~1.6 kHz.
Field activity was simultaneously sampled at a frequency of 133 Hz.
Each data segment was subjected to a real-time fast Fourier analysis
and classified as either or LIA by the following criteria: (1) was defined as a sinusoidal-like waveform with a peak frequency of 2-8
Hz and a small bandwidth, and (2) LIA was defined as a large-amplitude
irregular activity with a broad frequency band (0.5-25 Hz) (see Leung
et al., 1982). Analysis of digitized data samples provided the mean
discharge rate of a cell (in Hz) and an auto-correlation histogram
(ACH) of the discharge pattern of the cell. For cross-correlation
analysis, both the digitized field activity and the spike train were
converted to ASCII files and split into 512 bit (3.85 sec) segments.
Each spike train segment was convolved with a Gaussian kernel [ = 15 msec; the resulting spike density function (Ahmed and Rao, 1975;
Richmond et al., 1987) reflected the inter- rather than the intraburst
spike intervals] and cross-correlated relative to the hippocampal
field activity using a frequency-domain algorithm (Press et al., 1986).
Five segments were averaged to produce the final cross-correlation
function (CCF).
RESULTS
Cells localized to the PH, SuM, and MM were shown to have distinct
-related discharge patterns. The location of cells and examples of
their discharge patterns (analog oscilloscope traces) in LIA and are shown in Figure 1. The relationship of the discharge
of each type of cell to hippocampal EEG is shown in Figure
2. PH, SuM, and MM cells were classified in relation to
hippocampal field activity according to criteria that have been used
previously to classify cells in the hippocampal formation (Colom and
Bland, 1987; Bland and Colom, 1989), the entorhinal cortex (Dickson et
al., 1995), the MS/vDBB (Ford et al., 1989), and cingulate cortex
(Colom et al., 1988). All -related cells recorded in the PH
(n = 12) were found to be of the tonic -ON type
(i.e., they discharged tonically and at higher rates during hippocampal
elicited by RPO stimulation than during LIA; see Figs.
1B, 2A). All -related cells in the SuM
(n = 9) and MM (n = 15) were found to
be of the phasic -ON type (i.e., they discharge in rhythmic bursts
phase-locked to concurrent hippocampal activity and nonrhythmically
during LIA; see Figs. 1B, 2B,C).
Fig. 1.
A, Diagrammatic reconstruction
(Paxinos and Watson, 1982) of the location of classified cells in the
caudal diencephalon. Cells were localized in the various nuclei by an
examination of the histology showing pontamine sky blue deposits
ejected from the glass microelectrodes used to record the cells. Tonic
-ON cells (shown as black squares) were found in the
posterior hypothalamic nucleus (PH), phasic
-ON cells were found in the supramammillary nucleus
(SuM; black circles), and medial
mammillary nucleus (MM; black triangles).
B, Discharge patterns (1 sec oscilloscope traces) of PH,
SuM, and MM cells during spontaneous LIA (left side) and during theta
elicited by RPO stimulation. Calibration bar, 0.5 mV.
[View Larger Version of this Image (22K GIF file)]
Fig. 2.
A-C, Analyses used
to classify PH tonic -ON cells and SuM and MM phasic -ON cells.
Shown are the digitized field and cell activity (top
panels), auto-correlation histograms (ACH;
middle panels), and cross-correlation functions
(CCF; bottom panels) during hippocampal
LIA (left column) and RPO-elicited (right
column). A, PH cells show a nonrhythmic
discharge pattern during both and LIA conditions with a higher
discharge rate during the condition. The ACHs also indicate that
the cell discharged in a nonrhythmic pattern during the simultaneous
occurrence of either LIA or , and the CCF shows that the cell did
not discharge preferentially with respect to the phase of the
extracellular field activity. B, C,
The ACHs of SuM and MM cells show that they discharge in a nonrhythmic
pattern during LIA and a rhythmic pattern during RPO-elicited
hippocampal . The CCFs show that the cells discharged preferentially
on a particular phase of the extracellular wave. Calibration bar,
1.0 mV.
[View Larger Version of this Image (49K GIF file)]
Effects of septal procaine infusion
An illustrative example of the effect of septal procaine infusion
on the discharge of a PH tonic -ON cell is shown in Figure
3A. The mean of the responses (in terms of
discharge rate) of all PH tonic -ON cells to septal procaine
infusion is shown in Figure 4A. In the
preprocaine condition, hippocampal was elicited by RPO stimulation.
The rate of PH tonic -ON cell discharge increased relative to that
during LIA (see Figs. 2A, 3A,
Pre-Procaine). In the period immediately after
the procaine infusion, in which suppression of hippocampal was
maximal, not only was PH tonic -ON cell discharge still observed,
but the same level of RPO stimulation significantly
(t(1,11) = 3.6; p < 0.05;
Scheffé post hoc pairwise comparison) increased their mean
discharge rate relative to the preprocaine condition (Figs.
3A, 4A, Post-Procaine).
This was particularly evident in the illustrated cell (Fig.
3A). After 10-20 min, RPO stimulation again elicited clear
activity in the hippocampal field and the rate of tonic cell
discharge under stimulation returned to preprocaine levels (Figs.
3A, 4A, Recovery).
Fig. 3.
The effect of septal infusions of procaine on RPO
stimulation elicited hippocampal and -related PH
(A), SuM (B), and MM (C)
cell discharge. Shown are the digitized field and cell activity
(top panels) and auto-correlation histograms
(ACH; middle panels) in the preprocaine
condition (Pre-Procaine) during the abolition of
hippocampal immediately (1-3 min) after septal procaine infusion
(Post-Procaine) and when hippocampal returns, 10-30
min after the end of the procaine infusion (Recovery).
Calibration bar, 1.0 mV.
[View Larger Version of this Image (62K GIF file)]
Fig. 4.
A, Mean discharge rate of PH cells
(in the spontaneous condition and under RPO stimulation) before the
septal infusion of procaine (Pre Proc.), within a 5 min
period after the end of the septal procaine infusion in which
RPO-elicited hippocampal was completely abolished (Post
Proc.), and after RPO-elicited hippocampal had recovered to
preprocaine levels (Recovery). Spontaneous levels of PH
cell discharge were not significantly different across the preprocaine,
postprocaine, and recovery conditions. Under RPO stimulation, however,
significant differences in discharge rates were observed across
conditions (F(2,11) = 10.1;
p < 0.005). The discharge rate of PH cells under
RPO stimulation was significantly higher in the postprocaine condition
relative to that in the preprocaine or recovery conditions (both
p < 0.005; Scheffé post hoc pairwise
comparisons). B, Mean rhythmic burst frequency of SuM
cells during RPO stimulation before the septal infusion of procaine
(Pre Proc.), within a 5 min period after the end of the
septal procaine infusion in which RPO-elicited hippocampal was
completely abolished (Post Proc.), and after
RPO-elicited hippocampal had recovered to preprocaine levels
(Recovery). Significant differences in discharge rates
were observed across conditions (F(2,10) = 23.5; p < 0.0005). The rhythmic burst frequency of
SuM cells under RPO stimulation was significantly higher in the
postprocaine condition relative to that in the preprocaine or recovery
conditions (both p < 0.001; Scheffé
post hoc pairwise comparisons). C, Mean
rhythmic burst frequency of MM cells during RPO stimulation before the
septal infusion of procaine (Pre Proc.), within a 5 min
period after the end of the septal procaine infusion in which
RPO-elicited hippocampal was completely abolished (Post
Proc.), and after RPO-elicited hippocampal had recovered to
preprocaine levels (Recovery). There was no significant
difference in rhythmic burst frequency between the preprocaine and
recovery conditions. In the postprocaine period, rhythmic discharge was
not observed (NR).
[View Larger Version of this Image (22K GIF file)]
An illustrative example of the response of an SuM phasic -ON cell to
septal procaine infusion is shown in Figure 3B. In the
preprocaine condition, RPO stimulation elicits hippocampal and
phase-locked rhythmical SuM cell discharge. After septal procaine
infusion, hippocampal activity is abolished but RPO stimulation
continued to elicit rhythmical activity in SuM phasic -ON cells.
This is evident from the ACF of the cell (Fig. 3B,
Post-Procaine). Although SuM phasic -ON cells
survived septal procaine infusion, this manipulation was not without
effect. As can be seen in the example in Figure 2B (compare
ACH pre- vs postprocaine) and from the means in Figure 4B
(pre- vs postprocaine), RPO stimulation postprocaine elicited a
slightly higher burst frequency in SuM phasic -ON cells than the
same level of stimulation in the preprocaine condition. Although small,
the increase was found to be significant (t(1,8) = 5.1; p < 0.001; Scheffé post hoc pairwise
comparison). After 10-20 min postprocaine, clear hippocampal was
again elicited in response to RPO stimulation, and the frequency of
burst discharge returned to preprocaine rates (Figs. 3B,
4B, Recovery).
The response of MM phasic -ON cells to septal procaine infusion is
illustrated in Figure 3C. As with the SuM phasic -ON
cells, in the preprocaine condition RPO stimulation elicits rhythmical
MM cell discharge phase-locked to hippocampal . In contrast to PH
and SuM -ON cells in which discharge rates but not discharge
patterns were altered after septal procaine, septal procaine infusion
radically altered the discharge rate and pattern in MM cells. As can be
seen in Figures 3C and 4C, in the first 5 min
after septal procaine infusion (when the procaine block was maximally
effective) MM cell discharge was severely attenuated (and in some cases
abolished completely). This was the case for both spontaneous discharge
and that during RPO stimulation. After the initial attenuation (or
abolition) of MM cell discharge rates, spontaneous cell discharge rates
increased toward preprocaine levels. However, RPO stimulation did not
elicit rhythmical MM cell discharge patterns until clear -activity
was again observed in the hippocampal record.
DISCUSSION
In the present report, the dependence of -related single-unit
discharge of cells in the caudal hypothalamus on activity in the
septo-hippocampal system was assessed. Hippocampal activity was
elicited by RPO stimulation, and -related discharge patterns of
cells were classified according to previously used criteria. In accord
with the findings of our previous study (Bland et al., 1995),
-related PH cells were all found to be of the tonic -ON type
(i.e., they discharged tonically and at higher rates during hippocampal
than during LIA), whereas all -related SuM and MM cells were of
the phasic -ON type (i.e., they discharge rhythmically and
phase-locked to concurrent hippocampal activity, and
nonrhythmically during LIA). Subsequently, the discharge patterns of
the cells in response to RPO stimulation were tested after hippocampal
was abolished by septal procaine infusion. It was found that
-related cells in different nuclei were differentially affected by
the abolition of .
The response of tonic PH -ON cell discharge to RPO stimulation
(i.e., increases in tonic discharge rate) survived after the abolition
of by infusion of procaine into the septum. Furthermore, there was
a significant increase in discharge rate during stimulation after
procaine infusion relative to that during stimulation in the
preprocaine condition. Similarly, rhythmic SuM phasic -ON cell
discharge in response to RPO stimulation was still observed after the
abolition of hippocampal by septal procaine infusion. Again,
however, septal procaine was not without effect. The burst frequency of
SuM phasic -on cells during stimulation after procaine was slightly
(but significantly) higher than that seen during stimulation before
procaine.
These data indicate that the increases in discharge rate of PH tonic
-ON cells and the rhythmic discharge of SuM phasic -ON cells
during hippocampal are independent of activity in the
septo-hippocampal system. This supports previous suggestions that the
PH and SuM are both relays in an ascending ``-synchronizing''
system from the RPO to the MS/vDBB, and that PH tonic -ON and SuM
phasic -ON cells act in synergy in the generation of hippocampal
. It has been suggested (Kirk and McNaughton, 1991, 1993) that the
level of ascending tonic RPO input is transduced into the frequency of
in the SuM (reflected in the frequency of SuM cell burst
discharge), and that this frequency-coded information is then fed via
the medial forebrain bundle (Veazy et al., 1982; Vertes, 1992) to the
MS/vDBB. The PH, however, may provide tonic input (possibly
cholinergic; see Brazhnik and Vinogradova, 1986; Oddie et al., 1994;
Bland et al., 1995) to the MS/vDBB and hippocampus that accentuates
rhythmic firing in septal cells (Brazhnik and Vinogradova, 1986; Bland
et al., 1994) and is required for the expression of field activity
in the hippocampus (Oddie et al., 1994).
The fact that after septal procaine infusion the rate of PH tonic
-ON cell discharge and the frequency of bursts of SuM phasic -ON
cells both increase during stimulation suggests that -related PH and
SuM cell discharge are normally subject to descending modulatory or
rate-limiting influences from the septo-hippocampal system (on the
basis of SuM multiunit activity after septal procaine, we have
suggested previously that this may be true for the SuM (Kirk and
McNaughton, 1991). Phasic -ON cells in the SuM may also be involved
in a mutual resonant interaction with those in the septo-hippocampal
system during hippocampal . This may result in phasic SuM cells
being entrained to a lower burst frequency than would be the case if
they were solely under the influence of input ascending from the
midbrain. Miller (1991) has suggested previously an involvement of
resonant loops in activity in other parts of the system (see also
Bland and Colom, 1993).
Neither the origin nor the hypothalamic targets of the descending
influence from the septo-hippocampal system are known. Because of
diffusion (Myers, 1966), the volume of septal procaine infused (2.0 µl) is likely to abolish or severely attenuate -related discharge
in a considerable region of the septal complex and, because of its
dependence on septal projections, that in the hippocampus and
parahippocampal areas as well (for review, see Miller, 1991). However,
the lateral septum, which receives projections from hippocampal CA3
region (Swanson and Cowan, 1977; Leranth et al., 1992), sends
descending projections to the SuM (Swanson and Cowan, 1979) and other
diencephalic nuclei (Swanson and Cowan, 1979; Leranth et al., 1992).
Thus, the lateral septal area may relay descending modulatory signals
to PH and SuM during hippocampal . As has been suggested previously,
the descending influences may target a population of tonic -OFF
cells found in the border region between PH and SuM (Bland et al.,
1995). It is also possible that the MM (in receipt of descending
influences from the septo-hippocampal system, see below) mediates
activity in PH and SuM. MM has been shown to project to surrounding
hypothalamic regions including SuM and PH (Gonzalo-Ruiz et al., 1991).
Clearly, more work is needed to distinguish between these
possibilities.
It should be noted that whereas procaine infused into the SuM
attenuated the amplitude and frequency of reticularly elicited
hippocampal in urethane-anesthetized (Kirk and McNaughton, 1993;
Thinschmidt et al., 1995) and unanesthetized (McNaughton et al., 1995)
rats, lesions of the SuM did not appear to affect spontaneous and
movement-related in the unanesthetized animal (Thinschmidt et al.,
1995). It seems likely, therefore, that, as has been suggested
previously, rhythmical activity in SuM is not necessary for the
expression of per se (Kirk and McNaughton, 1993; Bland et al.,
1995; Thinschmidt et al., 1995). Further, it has been demonstrated that
lesions of the RPO produced little obvious change in hippocampal in
freely moving animals (Farris and Sainsbury, 1990). Hence, it is
possible that the SuM is involved in the modulation of frequencies
only when in receipt of high levels of activation from the RPO that may
normally only occur in particular behavioral states (Vertes, 1982,
1986) or, as in the present study, during RPO stimulation. Input from
the PH may be particularly important for the expression of generally (see above). However, a variety of other pathways may be
involved also. For example, cells of the pedunculopontine tegmentum
(PPT) also project directly to the MS/vDBB (Woolf and Butcher, 1986),
and stimulation of (Vertes, 1982), or infusion of carbachol into
(Vertes et al., 1993b) the PPT has been shown to effectively elicit
.
In contrast to PH and SuM -ON cells, the discharge properties of MM
phasic -ON cells were considerably affected by septal procaine
infusion. Not only was the discharge of MM phasic-ON cells nonrhythmic
during RPO stimulation after septal procaine, but discharge rates were
severely attenuated immediately after septal procaine infusion. The
loss of rhythmic discharge of MM cells after septal procaine supports
the results of partial coherence analysis suggesting that rhythmical,
-related MM discharge (but not that of SuM) is driven by descending
inputs originating in the hippocampal formation (Kocsis and Vertes,
1994). As noted above, the MM is likely to receive descending input
originating in the hippocampus and relayed via the subiculum (Swanson
and Cowan, 1975, 1977; Allen and Hopkins, 1989). The MM projects
heavily to the anterior thalamus (Veazy et al., 1982) and may be
involved in relaying -frequency activity from the septo-hippocampal
system to the anterior nucleus of the thalamus (Alonso and
Llinás, 1992). In turn, the anterior thalamus may relay, as
Kocsis and Vertes (1994) note, -frequency activity back to the
hippocampus via the cingulate and entorhinal cortices. Thus, activity may be transmitted around the circuit originally described by
Papez (1937). However, the MM is also in receipt of projections from
the entorhinal cortex (Shibata, 1988) and medial septum (Swanson and
Cowan, 1979).
The attenuation of MM discharge rates after septal procaine indicates
that MM cell discharge per se is largely dependent on descending input
from the septo-hippocampal system. During -activity, descending
input from the septo-hippocampal system may counteract inhibitory
GABAergic influences to MM ascending from the midbrain (Tappaz and
Brownstein, 1977; Stratford and Wirtshafter, 1989) or from the
tuberomammillary nuclei (Gonzalo-Ruiz et al., 1992). MM cells in
vitro (lacking extrinsic sources of modulation) can discharge in
rhythmic (albeit sub--range) bursts (Alonso and Llinás, 1992).
During -activity in vivo, descending septo-hippocampal
influences may act to overcome any tonic inhibitory input to MM and to
entrain the endogenous rhythmic activity of MM cells to frequencies.
In summary, the single-unit work reported here has demonstrated that
tonic -ON cell discharge in PH, and phasic -ON cell discharge in
SuM, is not dependent on input descending from the septum or
hippocampus during activity. This supports the idea that the PH and
SuM form relays in the ascending -synchronizing system. The present
study has also documented for the first time that MM phasic -ON cell
rhythmic discharge, and discharge per se, is largely dependent on input
descending from the septo-hippocampal system during . Finally,
although descending input from the septo-hippocampal system to PH and
SuM is not required for -related activity in these structures, we
provide evidence for descending, modulatory influences from the
septo-hippocampal system to both PH and SuM.
FOOTNOTES
Received April 18, 1996; revised June 5, 1996; accepted June 11, 1996.
This work was supported by Natural Sciences and Engineering Research
Council (NSERC) Grant A9935 to B.H.B., a University of Calgary
Post-Doctoral Fellowship to I.J.K., and an Alberta Heritage Foundation
for Medical Research Post-Graduate Scholarship to S.D.O. J.K. was a
visiting scientist supported by funds from NSERC. We thank Karen Waldie
for comments on this manuscript.
Correspondence should be addressed to Brian H. Bland, Department of
Psychology, Behavioral Neuroscience Research Group, The University of
Calgary, Calgary, Alberta, Canada T2N 1N4.
Dr. Konopacki's current address: Department of Neurobiology,
University of Lód , 66 Rewolucji 1905r Street, 90-222 Lód, Poland.
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