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The Journal of Neuroscience, October 1, 1999, 19(19):8616-8622
Reduced Synaptic Facilitation between Pyramidal Neurons in the
Piriform Cortex After Odor Learning
Drorit
Saar1,
Yoram
Grossman1, and
Edi
Barkai2
Departments of 1 Physiology and
2 Morphology, Faculty of Health Sciences and Zlotowski
Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva
84105, Israel
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ABSTRACT |
Learning-related cellular modifications were studied in the rat
piriform cortex after operand conditioning. Rats were trained to
discriminate positive cues in pairs of odors. In one experimental paradigm, rats were trained to memorize 35-50 pairs of odors
("extensive training"). In another paradigm, training was continued
only until rats acquired the rule of the task, usually after learning
the first two pairs of odors ("short training").
"Pseudotrained" and "naive" rats served as controls. We have
previously shown that "rule learning" of this task was accompanied
by reduced spike afterhyperpolarization in pyramidal neurons in brain
slices of the piriform cortex. In the present study, synaptic inputs to the same cells were examined. Pairs of electrical stimuli applied to
the intrinsic fibers that interconnect layer II pyramidal neurons revealed significant reduction in paired-pulse facilitation (PPF) in
this pathway even after short training. PPF in shortly trained rats was reduced to the same extent as in extensively trained rats. PPF
reduction did not result from modification of membrane properties in
the postsynaptic cells, change in postsynaptic inhibition, or
impairment of the facilitation mechanism. Extracellular field potential
recordings showed enhanced synaptic transmission in these synapses. The
reduction in PPF became apparent only 3 d after task acquisition
and returned to control value 5 d later. PPF evoked by stimulating
the afferent fibers to the same neurons was increased 1 d after
training for 2 d. We suggest that the transient enhancement in
connectivity in the intrinsic pathway is related to the enhanced
learning capability and not to memory for specific odors, which lasts
for weeks.
Key words:
odor learning; operand conditioning; paired-pulse
facilitation; piriform cortex; synaptic enhancement; pyramidal
neurons
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INTRODUCTION |
The idea that memory is manifested
at the cellular level by enhancement of synaptic connections between
simultaneously activated neurons was suggested half a century ago
(Hebb, 1949 ) and has been widely accepted since then (for review, see
Bliss and Collingridge, 1993; Hawkins et al., 1993). However,
behaviorally induced synaptic changes have been demonstrated only
lately, both in vivo (Ahissar et al., 1992; Wilson and
McNaughton, 1994; Rioult-Pedotti et al., 1998) and in vitro
(Mackernan and Shinnick-Gallagher, 1997; Power et al., 1997;
Rioult-Pedotti et al., 1998). These last in vitro studies
have demonstrated that learning-related synaptic modulations can be
preserved and detected in brain slices.
The rat olfactory modality offers significant advantages for the study
of learning-related synaptic modifications. Rats, for whom olfaction is
a dominant sensory modality, can easily learn to discriminate between
positive and negative cues in pairs of odors. Furthermore, rats
demonstrate capability for rule learning of odor discrimination [e.g.,
interproblem learning that occurs when performing a series of
discrimination problems with the same method of solution (Nirson et
al., 1975)]. Thus, they can acquire large amount of olfactory
information in discrimination tasks in a relatively short time (Saar et
al., 1998). In addition, by applying "reversal test" (presenting
previously learned odors with reversed significance), Staubli et al.
(1987) demonstrated that rats can reliably recall previously learned
odors few weeks after training, even if additional odor memory was
acquired during that time.
The piriform cortex is the largest cortical area receiving direct input
from the olfactory bulb, via the lateral olfactory tract (LOT), without
thalamic intermediation. The inputs of the olfactory nerve are
nontopographically spread across the entire surface of the piriform
cortex. Accordingly, presentation of eight different odors to rats
resulted in increased firing rate in >30% of the piriform cortex
cells, with each cell responding to at least one of the odors
(Schoenbaum and Eichenbaum, 1995a).
Activity-dependent plasticity in the piriform cortex has been reported
in several studies. Synaptic activity evoked in the piriform cortex by
stimulating the LOT is strongly enhanced by olfactory training (Roman
et al., 1987, 1993; Litaudon et al., 1997). LTP can be readily induced
in the piriform cortex in vitro (Jung et al., 1990; Kanter
and Haberly, 1990, 1993; Jung and Larson 1994; Hasselmo and Barkai,
1995) and in vivo (Stripling et al., 1988, 1991). The
piriform cortex has a simple and defined anatomical organization
(Price, 1973; see also Fig.
1C). Pyramidal cell bodies are
densely packed in a thin layer (layer II), with the intercortical association axons synapsing on the proximal zone of the apical dendrites (layer Ib), and the afferent input axons of the LOT synapsing
on the distal part of the apical dendrites (layer Ia). This laminar
organization enables recording from a homogenous population of neurons
and stimulating specific synaptic pathways.
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Figure 1.
Training for odor discrimination and recording
from cortical brain slices. A, Schematic description of
the four-arm maze. Protocols for trained and pseudotrained rats were
similar: an electronic "start" command opens randomly two of eight
valves (V), releasing a positive-cue odor
(P) into one of the arms and a negative-cue odor
(N) into another. Eight seconds later, the two
corresponding guillotine doors (D) are lifted to
allow the rat to enter the selected arms. After reaching the far end of
an arm (90-cm-long), the rat body interrupts an infrared beam
(I, arrow), and a drop of drinking water
is released from a water hose (W) into a
small drinking well (for a trained rat, only if the arm contains the
positive-cue odor; for a pseudotrained rat, randomly). A trial ends
when the rat interrupts a beam, or in 10 sec, if no beam is
interrupted. A fan is operated for 15 sec between trials, to remove
odors. B, Trained rats demonstrated acquisition of rule
learning. Seven consecutive days of training were required for this
group to reach criterion for discriminating between the first pair of
odors (80% correct choices). Discrimination between any new pair of
odors, starting from the third and fourth pairs could be reached
within 1 d. Values represent mean ± SE.
n = 11 rats. Results were similar for other rat
groups that were trained subsequently. C, Schematic
illustration of the piriform slice and the experimental procedure. The
pyramidal cells located in layer II receive excitatory afferent input
from LOT at the distal dendrites (layer Ia) and
excitatory intrinsic input from other cortical pyramidal cells at the
proximal dendrites (layer Ib). Intracellular recordings
were performed from cell bodies in layer II. Field potentials were
recorded in layer Ib.
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We have previously demonstrated that rule learning of an odor
discrimination task is accompanied by increased excitability in
pyramidal neurons in layer II of the piriform cortex, caused by reduced
spike afterhyperpolarization (Saar et al., 1998). We report now that
synaptic transmission between these neurons is also enhanced after
acquisition of the same task. Furthermore, we show that this
pathway-specific synaptic enhancement is transient, and thus cannot
underlie long-term memory storage.
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MATERIALS AND METHODS |
Animal training
Subjects. Young adult Sprague Dawley male rats were
used. Before training they were maintained on a 23.5 hr water
deprivation schedule, with food available ad libitum.
Apparatus and odors. Olfactory discrimination training
protocol was performed in a four-arm radial maze (Fig.
1A), with commercial odors that are regularly used in
the cosmetics and food industry.
Training. Olfactory training consisted of 20 trials per day
for each rat. Learning was considered as acquired after demonstration of at least 80% positive cue choices in the last 10 trials of the day.
The control rats were either exposed to the same protocol of training,
but with random water rewarding (pseudotrained) or were water-deprived,
with no training (naive). Once discrimination between a pair of odors
was acquired by all the rats in the trained group, on the next day both
trained and pseudotrained groups resumed training with a new pair of
unfamiliar odors. As we previously reported (Saar et al., 1998), our
training study confirms the original report by Staubli et al. (1987)
that once the rats reach good performance with the first pair of odors,
their capability to distinguish between new odors increased (Fig.
1B). These data suggest an important implication:
training to distinguish between the first pair of odors results not
only in memory acquisition of these particular odors, but with the
ability to acquire odor memory much faster. Therefore, one may
speculate that rule learning was also acquired. According to the
experiment, some rats were trained with two or three pairs of odors, to
ensure rule learning (short training). Others were trained with up to
50 pairs of odors (extensive training).
Slice preparation, stimulation, and recording
Rats were killed at several different time periods after
training completion. Four hundred micrometer coronal brain slices were
cut as previously described (Barkai and Hasselmo, 1994) and kept in
oxygenated (95% O2 plus 5%
CO2) Ringer's solution (in mM: NaCl
124, KCl 3, MgSO4 2, NaH2PO4 1.25, NaHCO3 26, CaCl2 2, and
glucose 10). Tungsten electrodes were placed in layer Ib to stimulate
the intrinsic fibers and in layer Ia to stimulate the afferent fibers
(Fig. 1C). Electrical stimuli were applied at 0.1 Hz.
Intracellular recordings were performed at 36°C with 4 M K-acetate-filled sharp electrodes. The
amplitudes of the responses were measured from digital averaging of 10 consecutive responses. To standardize the intracellular recording
conditions, stimulus intensity was adjusted so that the averaged
amplitude of 10 consecutive PSPs in the recorded cell would be 10 mV at
Vm =  80 mV, and the same stimulus intensity was used
for all paired pulse facilitation (PPF) measurements in that cell.
Extracellular recordings were performed with Ringer's solution-filled
electrodes at lower temperature (34°C), to allow temporal separation
between the presynaptic and postsynaptic responses.
The identity of rats (naive, trained, or pseudotrained) was not known
to the person conducting the experiments and the analysis.
Statistical analysis
One-way ANOVA was used to evaluate significance of difference
among three cell populations. Student's t test was used to
compare between each two cell populations.
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RESULTS |
Extensive training
The kinetics of single PSPs in the intrinsic synapses are not
modified by training
We have previously shown that basic membrane properties such as
resting potential, input resistance, and membrane time constant in
layer II pyramidal neurons are not modified after extensive training
(Saar et al., 1998). The kinetics of single, standardized (10 mV
amplitude at Vm = 80 mV) postsynaptic potentials,
evoked by stimulating the intrinsic pathway to these neurons, were also similar in all groups (Table 1). These
data suggest that the learning-related modifications in the dynamics of
these synaptic responses, as will be described, are not the result of
changes in membrane properties of the postsynaptic neurons.
PPF in the intrinsic synapses is decreased after training
Pairs of stimuli, separated by short intervals, may result in
amplification of the second response in a pair. This phenomenon, termed
PPF, is thought to reflect enhanced synaptic release during the second
response, caused by residual Ca2+
accumulation in the presynaptic terminal (Katz and Miledi, 1968; Wu and
Saggau, 1994). Pyramidal cells in the piriform cortex exhibited PPF
when interstimulus intervals (ISI) ranged between 50 and 150 msec. For
this whole range, PPF was markedly smaller in cells from the trained
rats than in cells from pseudotrained and naive rats (Fig.
2A,B). The SD of PPF
distribution for the trained group was not larger than for the other
groups. For example, at ISI of 50 msec the values of PPF were 1.33 ± 0.21, n = 20 for the naive, 1.19 ± 0.17, n = 20 for the trained, and 1.37 ± 0.24, n = 13 for the pseudotrained group. This indicates that
PPF reduction was apparent in most of the neurons sampled in trained
rats, rather than in a subgroup of these neurons, as demonstrated in
the cumulative frequency distribution of PPF values (Fig.
3A). Figure 3B
demonstrates that PPF reduction became prominent 1 d after
extensive training completion and remained so until 6 d after the
training. Dysfunction of the PPF mechanism after intense training was
ruled out by perfusing the slices from trained rats with low
[Ca2+] (0.5 mM)
solution, as a result of which the first EPSP was reduced, and PPF was
enhanced (n = 3; Fig.
4A).
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Figure 2.
Reduced PPF in piriform cortex of extensively
trained rats. Each group entailed seven rats. Rats were killed
1-6 d after training completion. A, PPF was maximal at
ISI = 50 msec and decreased with larger intervals. For each ISI
between 50 and 150 msec, the averaged PPF measured in neurons from
trained rats was significantly smaller compared to that in neurons from
naive and pseudotrained (*p < 0.04) rats. PPF was
determined by calculating the ratio between the amplitude of the second
and first PSPs
(PSP2/PSP1) in digitally
averaged 10 consecutive responses. When the second PSP overlapped the
late part of the first, its baseline was estimated by digitally
subtracting a trace of averaged 10 single PSPs evoked in the same cell.
Each value represents mean ± SE. n = number
of neurons. One to four neurons were recorded form each animal in the
trained and naive groups, and one to three neurons were recorded from
each animal in the pseudotrained group. Inset, A typical
average of 10 responses to pairs of stimuli applied at 0.1 Hz with
ISI = 50 msec. B, PPF in trained and naive rats
(same neurons as in A) presented as percent of PPF in
neurons from the pseudotrained group ((PPF 1/PPFpseudo 1)*100). PPF in trained rats was reduced to
50-75% of PPF value in the pseudotrained rats (*p < 0.04), whereas PPF in naive rats did not significantly differ from
the pseudotrained. Values represent mean ± SE.
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Figure 3.
PPF reduction after extensive training is apparent
in most neurons. A, Cumulative frequency distribution of
PPF values at ISI = 50 msec (each point represents PPF in one
cell, the same cells as in Fig. 2A). The curve of
PPF values in trained rats is smoothly shifted to the left, indicating
that PPF reduction occurred in most of the sampled neurons and not in a
subgroup. B, Dynamics of PPF decrease (ISI = 50 msec). PPF in neurons from the trained rats (same neurons as in Fig.
2A) presented as percent of the averaged PPF in
neurons from the pseudotrained rats, and grouped according to the time
periods after training completion: three rats after 1 d, two rats
after 3 d, one rat after 4 d, and one rat after 6 d. PPF
reduction was prominent 1 d after training completion and remained
so until 6 d after the training. The apparent gradual decrease
from day 1 to day 6 was not significant, and thus the results were
lumped together in the curve in A. Values represent
mean ± SE. n = number of cells.
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Figure 4.
Properties of PPF reduction. A,
Effect of low [Ca2+]o on PPF in neuron
from trained rat. The first response of the neuron to a pair of stimuli
in normal [Ca2+]o (2 mM,
top trace) was reduced when the neuron was perfused with
low [Ca2+]o solution (0.5 mM, middle trace). Superimposition of the
two traces after normalizing the amplitudes of the first PSPs in both
(bottom) reveals that PPF was increased.
B, Evoked postsynaptic late inhibitory conductance does
not change after training. Top, The left
trace demonstrates a typical response to paired stimuli,
ISI = 150 msec. Superimposition (right) reveals
that the second response (dots) decays faster than the
first (line), suggesting that the first stimulus has
evoked a late postsynaptic shunting conductance. Bar
graph, The ratio between decay time constants of the second and
the first PSPs did not differ between groups, suggesting that the late
postsynaptic conductance did not change after training. Values
represent mean ± SE. n = number of
cells.
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PPF in the intrinsic synapses is not reduced by increased
postsynaptic conductance
EPSPs evoked by stimulation of the intrinsic fibers in the
piriform cortex are usually followed by a fast,
GABAA-mediated IPSP, and a late,
GABAB-mediated IPSP, which is at its peak 150 msec after stimulation (Tseng and Haberly, 1988). Indeed, the decay
rate of the second EPSP was always faster compared to that of the first
EPSP, indicating increased membrane conductance in the postsynaptic
cell during the second EPSP. This raises the possibility that a slow
postsynaptic conductance, initiated by the first stimulus of the pair,
underlies an apparent PPF reduction. However, the ratio between decay
rate of the second and the first EPSPs was similar for all groups (Fig.
4B), suggesting that the shunt caused by evoked
postsynaptic conductance was similar for all groups and could not
underlie the difference in PPF between the trained and the control rats.
Short training
PPF reduction in the intrinsic synapses is apparent also after
short training
The next set of experiments was aimed to determine whether PPF
reduction in the piriform cortex is correlated to the massive storage
of memory of many odors. To address this question, PPF was examined in
neurons from rats that were trained with only two pairs of odors, until
the dramatic enhancement in their capability to learn new odors was
demonstrated (Fig. 1B; Staubli et al., 1987; Saar et
al., 1998), but only few new odors are stored in memory. PPF with
ISI = 50 msec was compared among these shortly trained rats,
shortly pseudotrained, and naive rats. Averaged PPF values in the
shortly pseudotrained (mean ± SE, 1.33 ± 0.15; n = 38 cells) and in the naive (1.28 ± 0.22;
n = 23) groups were similar to each other and also
similar to the PPF values in extensively pseudotrained (1.37 ± 0.25; n = 13) and their matching naive (1.32 ± 0.12; n = 20) groups. PPF in the shortly trained group
reached a minimum value that was similar to the decrease previously
observed in extensively trained rats. Also, 8 d after training
completion PPF returned to control value (Fig.
5A). The values of PPF in neurons from trained rats at different time periods after training were
as follows: 1 d, 1.31 ± 0.14; 2 d, 1.31 ± 0.19;
3 d, 1.17 ± 0.14; 5 d, 1.11 ± 0.02; 7 d,
1.09 ± 0.05; 8 d, 1.30 ± 0.16; and 10 d,
1.32 ± 0.12.
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Figure 5.
PPF is reduced in the intrinsic, but not afferent
synaptic pathway after short training. Data obtained from 20 trained
and 14 pseudotrained rats. A, Dynamics of PPF decrease
in the intrinsic pathway after short training (stimuli applied to layer
Ib; ISI = 50 msec). Values of PPF in shortly trained rats are
presented as percent of the mean value of PPF in their matched shortly
pseudotrained rats. Trained rats were killed at different time periods
after training completion: four rats after 1 d, two rats after
2 d, four rats after 3 d, one rat after 5 d, two rats
after 7 d, five rats after 8 d, and two rats after 10 d.
Two to six neurons were recorded from each animal in the trained,
pseudotrained, and naive groups. Values represent mean ± SE.
n = number of cells. B, Dynamics of
PPF increase in the afferent pathway after short training. The same
cells as in A, with stimuli applied to layer Ia,
ISI = 50 msec. Values of PPF in the afferent pathway in trained
rats described as percent of the mean value in the same pathway in
pseudotrained rats. Values represent mean ± SE.
n = number of neurons.
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Cumulative frequency histograms show that here too, the PPF reduction
was detected in most of the sampled neurons and not in a subgroup (Fig.
6).
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Figure 6.
PPF reduction in the intrinsic pathway after short
training is observed in most sampled neurons. Cumulative frequency
distribution of PPF values at ISI = 50 msec. Each point represents
PPF in one cell, the same cells as in Figure 5A. PPF
values between 3 and 7 d did not differ significantly and
therefore are presented together. The curve of PPF values 3-7 d after
training completion is smoothly shifted to the left, indicating that
PPF reduction occurred in most of the sampled neurons and not in a
subgroup. The curve of PPF values in the first 2 d, and 8 d
or more after training completion did not differ from the curve of the
pseudotrained rats.
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Synaptic responses, but not axonal excitability is enhanced in the
intrinsic fibers
With short electrical stimulation applied to the intrinsic axons,
extracellular recordings in layer II reveal field potentials with two
separable components: a fast, short component, reflecting action
potentials in the activated axons (axon volley) and a slower component, which could be abolished by
Ca2+ removal, representing the PSPs
generated in the pyramidal neurons (Fig.
7A, top). As
stimulus intensity was increased, a linear increase was observed in
both components (Fig. 7A, bottom, B). The ratio
between stimulus intensity and the evoked axon volley did not differ
between trained and the control groups (Fig. 7C), indicating
that training did not alter the intrinsic axonal excitability in the
cortex. However, the ratio between field postsynaptic potential (fPSP) amplitude and axon volley increased significantly after training (Fig. 7D), indicating that the synaptic
transmission was enhanced.
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Figure 7.
Enhanced synaptic response in the intrinsic
pathway in shortly trained rats. Rats were killed 3-6 d after training
completion. A, Extracellular field potentials in
response to short stimulations of the intrinsic fibers. The axon volley
component is followed by a postsynaptic component
(fPSP). Top, Removal of
Ca2+ from the perfusing Ringer's solution (2 mM CaCl2 was replaced by 2 mM
MgCl2) resulted with increase of the axon volley and
complete abolishment of the fPSP. Bottom, In normal
Ringer's solution both components increase with increasing stimulus
intensity (up to 0.55 mA in this case). B, Example of
axon volley and fPSP amplitudes in response to different stimulus
intensities. Both components of the field potential show linear
relation to stimulus intensity. C, Averaged values of
the slopes of axon volley amplitude versus stimulus intensity. Slopes
were calculated by applying linear fits to the graphs as in
B. n = number of slices.
D, Averaged values of the slopes of fPSP amplitudes
versus axon volley amplitudes. Slopes were calculated by applying
linear fits to the graphs. The same slices as in C. Note
the significant difference between the trained group and the
pseudotrained and naive groups (*p < 0.05). Each
group entailed seven rats. One or two field potentials were recorded
from each animal.
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PPF increase in synapses of the afferent fibers
The profound enhancement in synaptic transmission after short
training raises the question whether it is a general arousal phenomenon
in the piriform cortex. Therefore, we examined the PPF of synaptic
responses evoked by stimulating the afferent axons terminating on the
same layer II pyramidal neurons. The synaptic potentials evoked by
stimulating at layer Ia, which contains these afferent fibers (Price,
1973), had PPF value of 1.21 ± 0.13 (n = 23)
in slices from pseudotrained and 1.22 ± 0.10 (n = 11) in naive rats. In contrast to the effect of training on PPF in the intrinsic pathway, PPF in the afferent pathway did not decrease after
rule learning acquisition. Rather, 1 to 2 d after training completion, PPF in the afferent pathway increased, and 3 d after training completion PPF in this pathway returned to control value (Fig.
5B). The values of PPF in neurons from trained rats at
different time periods after training were as follows: 1 d,
1.37 ± 0.09; 2 d, 1.36 ± 0.10; 3 d, 1.19 ± 0.13; 7 d, 1.18 ± 0.06; 8 d, 1.19 ± 0.10; 10 d, 1.29 ± 0.07.
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DISCUSSION |
Our data show that synaptic transmission between layer II
pyramidal neurons in the piriform cortex is altered after odor
learning. Although the basic kinetics of the single PSPs did not change even after extensive training, in consistence with our previous finding
that no changes occur in the intrinsic membrane properties of these
neurons (Saar et al., 1998), PPF evoked by stimulating the intrinsic
fibers was reduced after short odor training. In addition, the ratio
between field PSP and axon volley in the same pathway was increased
after training. Our findings suggest that synaptic transmission in the
intrinsic pathways is temporarily increased for several days after
short training.
The nature of enhanced synaptic connectivity
It has been shown previously that odor discrimination learning is
accompanied by potentiation in the piriform cortex (Roman et al., 1987,
1993) and that such modifications are spread over large areas of the
piriform cortex (Litaudon et al., 1997). Our data support these
findings. Gradual increase in the number of activated axons in the
intrinsic pathway resulted with significantly greater increase of the
fPSP in "trained" rats, compared to both controls, indicating
enhanced synaptic transmission. At the single cell level, PPF was
markedly reduced in neurons from trained rats, and this reduction was
not the result of increase in evoked postsynaptic conductance. Both
results indicate that the synaptic transmission enhancement is, at
least in part, the result of augmented synaptic release. i.e., the
release caused by the first stimulus in a pair is closer to its maximal
value, leaving less room for further facilitation of the second
response (Debanne et al., 1996). Indeed, when
[Ca2+]o was
reduced to decrease the release, PPF in slices from trained rats increased.
Specificity of modifications in synaptic transmission
to learning
The physiological changes observed in the cortex of the trained
animals were detected neither in the pseudotrained rats, which were
exposed to the same odors, nor in naive rats. This suggests that
exposure to odors or to the four-arm maze in itself is not sufficient
to generate the observed synaptic modifications (Saar et al., 1998),
rather they are correlated with the learning process. Furthermore, only
recent odor learning will be reflected in PPF reduction, because 8 d after training the effect disappears. Enhanced synaptic transmission
has been shown lately in brain slices from amygdala after fear
conditioning (Mackernan and Shinnick-Gallagher, 1997) and in
hippocampus after eyeblink conditioning (Power et al., 1997),
suggesting that learning-related enhancement in synaptic transmission
may be a general phenomenon that takes place in task-relevant regions
of the mammalian brain after different types of learning. Furthermore,
the reduction of PPF in the piriform cortex was specific to the
intrinsic pathway, suggesting that, as in the amygdala (Mackernan and
Shinnick-Gallagher, 1997), enhanced synaptic transmission in the
piriform cortex occurs at specific relevant sites and not throughout
the local cortical circuit.
That the reduced PPF occurs after extensive training to the same extent
as after short training may indicate that this modification reflects
the existence of enhanced learning capability. Alternatively, it may
reflect an ability to devote special attention to odor stimuli, which
becomes crucial for the trained rats.
Slow onset to maximal PPF reduction
The finding that PPF reduction after short training appears only
3 d after the last training session is of particular interest. One
possible explanation for this slow onset is that it reflects decreased
responsiveness in the olfactory system, which occurs as a result of
intense activity during odor learning, and fades out within 3 d
after the training. Such decreased responsiveness, manifested at the
synaptic level as reduced synaptic transmission, is consistent with the
transient increase in PPF in the afferent synaptic connections, which
appears 1 d after training and lasts for 2 d. The notion that
PPF increase in the afferent pathway reflects a temporary reduction in
synaptic transmission suggests that the afferent synapses are not
enhanced by training. However, if both processes occur in parallel in
the intrinsic pathway, the effect of synaptic potentiation on PPF would
be recorded only after the antagonist process is diminished.
Behavioral relevance of PPF reduction
We suggest that the observed PPF reduction in the intrinsic
pathway in the piriform cortex of odor-trained rats is related to the
phenomenon of enhanced learning rate after rule learning acquisition
rather than to memory storage of specific odors for the following
reasons: (1) PPF is significantly decreased after short training,
which results with rule learning acquisition, to the same extent as it
is decreased after memorizing many odors after extensive training (Fig.
8A), and was apparent
in most of the sampled neurons. Such a whole network modification is
suitable to serve increased information processing capability. It is
unlikely, though, that memory storage of two or many tens of odors will be represented by exactly the same quantitative decrease in PPF. (2)
Training suspension for 8 d or more results with PPF return to
pretraining values. We have previously shown that such a break in the
daily training routine results with reduced capability to learn new
odors (Saar et al., 1998). In contrast, rats can retrieve memory for
learned odors for at least 6 weeks after learning (Staubli et al.,
1987).
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Figure 8.
A, Cumulative frequency
distribution of PPF in shortly trained and extensively trained rats and
their matching pseudotrained groups (same data as in Figs.
3A and 6). Distribution of both trained groups are
similar, as is the distributions of both pseudotrained groups.
B, Time course of AHP reduction (Saar et al., 1998) and
PPF changes in the intrinsic and afferent pathways after short training
completion. Values are normalized to the averaged corresponding values
in pseudotrained rats.
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The question regarding the final location of long-term odor memory
storage remains open. One possibility is that long-term modifications
underlying memory also occur in the piriform cortex, but that synaptic
strengthening is mediated by increased number of synapses rather than
by physiological changes at single synapses. Another possibility is
that long-term memory modifications occur at a different brain area,
such as the orbitofrontal cortex, which is very active in odor learning
(Schoenbaum and Eichenbaum 1995a,b; Eichenbaum et al., 1996; Schoenbaum
et al., 1999).
Functional significance of the time window in which PPF
is reduced
Learning-dependent cellular modifications that lag the last
training session by 3 d were shown in dendrites of hippocampal pyramidal neurons after classical conditioning (Olds et al., 1989). Recently we have shown that short training results with increased excitability in pyramidal neurons in layer II of the piriform cortex,
caused by reduced spike afterhyperpolarization that can be detected
1 d after training and lasts for up to 3 d (Saar et al.,
1998). Taken together with the present results, it appears that these
two learning-related modifications, which emerge in sequence, with
partial overlap on the third day after training, can maintain
learning-related single-cell modifications for the combined period of
8 d. Accordingly, we suggest the following model for enhanced
learning capability in the mammalian brain: increased neuronal
excitability enhances neuronal activation, which consequently,
according to Hebb's rules, enhances synaptic transmission in the
intrinsic fibers, as reflected in reduced PPF (Fig.
8B). This transient synaptic enhancement does not
underlie long-term memory maintenance, but may serve as an intermediate stage, creating favorable conditions for long-term memory formation.
| |
FOOTNOTES |
Received March 1, 1999; revised July 14, 1999; accepted July 14, 1999.
This research was funded by a grant from the Israel Science Foundation.
Correspondence should be addressed to Dr. Edi Barkai, Department of
Morphology, Faculty of Health Sciences, Ben-Gurion University of the
Negev, Beer-Sheva 84105, Israel.
| |
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TOP
ABSTRACT
INTRODUCTION
