Functional development of hippocampal mossy fiber synapses in rabbits

The course of functional maturation with age of mossy fiber synapses on pyramidal cells in areas CA_3,4 of the dorsal hippocampus was investigated by extracellular recording of focal potentials and single unit responses of the hippocampus to electrical stimulation of the dentate fascia in waking, unimmobilized rabbits aged from 1 to 14 days. After the 4th day of postnatal life focal potentials appeared in response to single stimulation, in the form of a biphasic short-latency wave, characteristic of responses of the mature hippocampus, accompanied by spike discharges with a latent period of 3 to 10 msec and inhibitory responses of the hippocampal neurons. During the next 10 days the amplitude of the focal potentials increased from several hundred millivolts, with the sharpest increase observed from the 4th through the 7th days. In early age periods global and unitary responses were shown to be capable of frequency potentiation and also of short-term after-potentiation.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 12, No. 3, pp. 246–254, May–June, 1980.     

Posttetanic changes in hippocampal minimal evoked potentials

Changes in the EEG induced by a single spike were recorded in the hippocampus of an unanesthetized rabbit. Summation of focal electrical activity synchronous with spontaneous single unit discharges at the symmetrical point of contralateral hemisphere revealed no stable potentials which could reflect these changes. In two cases discharges identified as activity of Shaffer's collaterals were recorded in area CA₁. Summation of post-spike changes in evoked activity recorded by the same microelectrode showed stable negative waves with an amplitute of 40–60 µV, which could have been evoked by single spikes. The curve of amplitude of the averaged evoked potentials versus near-threshold current strength stimulating the intrahippocampal pathways was not smooth in most experiments but stepwise in character. It is suggested that the minimal evoked potential corresponding to the first step (amplitude 40–80 µV) reflects a response to stimulation of one fiber. After above-threshold tetanization prolonged posttetanic potentiation of the minimal evoked potentials did not arise in CA₁ in response to stimulation of Shaffer's collaterals. Minimal evoked potentials recorded in area CA₃ in response to stimulation of the dentate fascia showed clear potentiation. The results are in agreement with the hypothesis of the synaptic localization of the mechanisms responsible for prolonged posttetanic potentiation.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 9, No. 2, pp. 124–134, March–April, 1977.     

Investigation of heterosynaptic interactions in hippocampal areas CA1, and CA3 in vitro

Heterosynaptic interactions between synapses located at a considerable distance from the cell body (perforant path) and lying close to the body of the neuron (synapses of Schaffer's collaterals and axons of the dentate fascia) on guinea pig hippocampal neurons were investigatedin vitro. It was shown by the paired stimulus method that, using stimulation of subthreshold intensity for action potential generation, spatiotemporal summation takes place in both pairs of synaptic systems. If above-threshold stimulation was used, afferents lying close to the cell body suppressed responses evoked by stimulation of distant afferents for a longer time (up to 20 msec in area CA₁ and up to 300 msec in area CA₃) than during the opposite combination of stimuli (up to 3–8 msec). After tetanization of the dentate fascia depression of responses of area CA₃ neurons to stimulation of the perforant path was observed for 2–30 min. In the remaining cases, no significant prolonged heterosynaptic posttetanic changes were observed. The possible mechanisms of these interactions are discussed.Institute of Biophysics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 524–532, November–December, 1979.     

Effects of extracellular calcium on low frequency induced potentiation and habituation in the in vitro hippocampal slice preparation

The electrophysiological characteristics of frequency potentiation and habituation were investigated in two afferent systems of the in vitro hippocampal slice preparation. Low frequency stimulation (1 Hz) of the Schaffer collateral - commissural (Sch-comm) fibers results in a short-term potentiation of the amplitude and rate of rise of the EPSP and population spike responses recorded in the CA1 region. In contrast, 1-Hz stimulation of the perforant path (PP) evokes a short-term, habituation-like depression of the dentate granule cell EPSP and population spike. An inverse relationship was observed between stimulus intensity and the magnitude of frequency potentiation or habituation. Changes in afferent fiber volleys or general excitability of postsynaptic membranes did not contribute significantly to the development of either of these forms of short-term plasticity. Perfusion with a medium containing a high calcium - low magnesium concentration (4 mM Ca+2 and 1 mM Mg+2) produced a differential effect on CA1 and dentate evoked potentials. Following a 20-min exposure to this medium, the amplitude of CA1 potentials was increased while dentate responses were decreased. Frequency potentiation of CA1 responses and habituation of dentate responses were depressed or eliminated by the high calcium medium. The opposing influence of extracellular calcium on CA1 and dentate evoked potentials indicates a fundamental difference in the process of transmitter release in these systems, a characteristic that may contribute to the production of frequency potentiation and habituation.     

Frequency potentiation in the neonatal rabbit hippocampus

The formation of properties of frequency potentiation in the entorhinal afferent pathway of the hippocampus was studied in unanesthetized rabbits aged from 1 to 15 days. In areas CA₁ and CA₃ of the dorsal hippocampus in newborn rabbits repetitive (1–20 Hz) electrical stimulation of the perforant path led to an increase in amplitude of the slow wave of the field potential by 20–100% compared with the control and to an increase in the probability of response discharges from the neurons from 0–0.5 in the control to 0.8–1.0 during tetanization. In rabbits aged 2–3 days potentiation was more marked at a frequency of 4–6 Hz, whereas depression of the responses developed rapidly to a higher frequency of stimulation. The frequency optimum of 4–15 Hz was established on the 5th day. Potentiation of the first component of the field potential was observed starting from the 8th–10th day of life. The experimental results show that the property of frequency potentiation in the cortical afferent connections of the hippocampus is found in rabbits actually at birth, and it acquires the adult form at the beginning of the second week of life.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 533–539, November–December, 1979.     

Synaptic plasticity at archicortical and neocortical levels

Research carried out by the author and his collaborators, devoted to analysis of the properties and neurophysiological mechanisms of long-term (for several hours) potentiation, is surveyed. Long-term potentiation of focal potentials and unitary responses of strictly hippocampal structures (areas CA₁ and CA₃) in the unanesthetized rabbit is described. Enhancement of excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials was found after tetanization. No corresponding changes of sensitivity to acetylcholine or acetylcholinesterase activity were found by microiontophoretic and histochemical methods during long-term potentiation. Statistical analysis of EPSPs evoked by microstimulation, based on the quantal hypothesis of synaptic transmission, showed an increase in the number of quanta of transmitter release during potentiation. Long-term potentiation of focal potentials during stimulation of the subcortical white matter in surviving neocortical slices and also long-term potentiation of focal and unitary responses of the sensomotor cortex of the unanesthetized rabbit are described. Potentiation of the "indirect" component of the global response of the pyramidal tract was found. The data suggest the presence of long-term potentiation of monosynaptic neocortical responses. It is concluded that the main mechanism of both hippocampal and neocortical long-term potentiation is increased efficiency of excitatory synapses. It is postulated that synapses modified in this way are used in the formation of memory traces.Brain Institute, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 16, No. 5, pp. 651–665, September–October, 1984.     

Formation of spontaneous and evoked unit activity in organotypical hippocampal tissue culture

Spontaneous and evoked single unit activity of Ammon's horn and the dentate fascia was investigated by extracellular recording in organotypical explants of neonatal mouse hippocampus during the first 2 weeks in culture. Three main types of spontaneous activity were observed: single, group, and volley. After the fifth to sixth day in culture the neurons were found to respond to stimulation of the entorhinal cortex and dentate fascia. Both short-latency (evidently monosynaptic) and long-latency responses were observed, and they usually varied if the stimulus was repeated. The appearance of evoked unit activity in the explants is considered to be due to maturation of synaptic contacts at axon endings of granule cells and perforant path, the formation of which continues during culture.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 257–266, May–June, 1977.     

Time course of changes in long-term potentiation of synaptic transmission following subcortical deafferentation on the rat hippocampus.

Brief tetanic stimulation potentiates synaptic transmission both in the CA1 and dentate area of slices cut from normal rats. This long-term potentiation (LTP) was assayed in slices made at various times from rats subjected to complete bilateral sectioning of all subcortical afferents which enter the hippocampus. Over about one week survival time, LTP is present in the CA1 region of all and also in the fascia dentata of about 50% of slices. We found no signs of LTP in the dentate area of slices cut over 8 weeks after deafferentation, while the responses were clearly potentiated in the CA1 area of the same slices. Four week was the longest period when a somewhat modified version of LTP could be produced in the subcortically deafferented dentate area. The results confirm previous reports that subcortical afferents mediate some unknown factors essential for maintenance of long-term plasticity of intrinsic synapses in the fascia dentata. This unidentified, perhaps trophic influence diminishes in about 4 weeks after severing the subcortical fibers. In contrast, maintenance of subcortical inputs are apparently not required for the LTP in the intrinsic CA1 synapses.     

Excitatory postsynaptic potentials of hippocampal neurons and their extinction during repeated stimulation

A method of detecting "minimal" excitatory postsynaptic potentials (EPSP) in neurons of hippocampal area CA₃ of the unanesthetized rabbit during stimulation of the septo-fimbrial region and the dentate fascia is described. The method consists of presenting a strong (a current of up to 1 mA) conditioning stimulus, inducing a distinct inhibitory postsynaptic potential (IPSP), before a near-threshold (current of 0.03–0.35 mA) testing stimulus. The response to the testing stimulus, develoing after the previous conditioning IPSP, in most cases was purely depolarizing and, judging from the change in the latent period in some cases and the absence of correlation between its amplitude and that of the IPSP, it is a pure EPSP. If the testing stimuli are presented at low enough frequency (intervals of not less than 1 sec) the amplitude of the EPSP evoked by them gradually falls. This decrease exhibits some of the characteristic properties of extinction of behavioral responses (recovery after an interruption, a more rapid decrease during repeated series of stimuli, a slower decrease in amplitude during less frequent stimulation). The amplitude of the IPSP also fell or showed no significant change. The results are evidence in support of the hypothesis that extinction is based on a mechanism of homosynaptic depression.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 10, No. 1, pp. 3–12, January–February, 1978.     

Functional characteristics of the mature and developing brain following neuroimmunization: an analysis of the short-term plasticity of the rat hypothalamus

In experiments on mature and developing (3-4 weeks old) rats the influence was shown of neuroimmunization with summate antigens of hippocampal or neocortical tissue cytosolic fraction on short-term plasticity of hippocampal CA3 field potentials under dentate gyrus zone stimulation. An increase of paired facilitation and frequency potentiation was revealed in pyramidal layer responses of hippocampal tissue immunized animals. In case of immunization with neocortical antigens the changes were less expressed, had mainly the opposite direction and took place in the apical dendrites zone. In young animals besides antigen spectrum depending effects of neuroimmunization an earlier manifestation (in comparison with age norm) of some focal activity definitive properties was described. The suggestions are made about different localization of hippocampal or neocortical tissue immunization "targets" with possible preferential damage of intrahippocampal systems when using this structure antigens, and also about dependence of physiological consequences on the extent of target structure ontogenetic maturity.     

Repetitive paired stimulation of nasotrigeminal and peripheral chemoreceptor afferents cause progressive potentiation of the diving bradycardia

Hallmarks of the mammalian diving response are protective apnea and bradycardia. These cardiorespiratory adaptations can be mimicked by stimulation of the trigeminal ethmoidal nerve (EN5) and reflect oxygen-conserving mechanisms during breath-hold dives. Increasing drive from peripheral chemoreceptors during sustained dives was reported to enhance the diving bradycardia. The underlying neuronal mechanisms, however, are unknown. In the present study, expression and plasticity of EN5-bradycardias after paired stimulation of the EN5 and peripheral chemoreceptors was investigated in the in situ working heart-brain stem preparation. Paired stimulations enhanced significantly the bradycardic responses compared with EN5-evoked bradycardia using submaximal stimulation intensity. Alternating stimulations of the EN5 followed by paired stimulation of the EN5 and chemoreceptors (10 trials, 3-min interval) caused a progressive and significant potentiation of EN5-evoked diving bradycardia. In contrast, bradycardias during paired stimulation remained unchanged during repetitive stimulation. The progressive potentiation of EN5-bradycardias was significantly enhanced after microinjection of the 5-HT(3) receptor agonist (CPBG hydrochloride) into the nucleus tractus solitarii (NTS), while the 5-HT(3) receptor antagonist (zacopride hydrochloride) attenuated the progressive potentiation. These results suggest an integrative function of the NTS for the multimodal mediation of the diving response. The potentiation or training of a submaximal diving bradycardia requires peripheral chemoreceptor drive and involves neurotransmission via 5-HT(3) receptor within the NTS.     

The septo-hippocampal pathway: electrophysiological observations

In 40 rats immobilized with gallamine evoked field potentials were elicited in the dorsal hippocampus by stimulation of the septal nuclei. Latency of the septohippocampal evoked potential (SHEP) elicited by stimulation of the medial septal nuclei, the variations of latencies and amplitudes with increasing stimulus intensities as well as the occurrence of frequency potentiation and post-tetanic potentiation allow the conclusion that the SHEP registered in the stratum granulare of dentate gyrus is mainly monosynaptically elicited. Nevertheless some data discussed in the paper point to the existence of a more complicated and not exclusively monosynaptic activation of granular cells caused by septal stimulation.     

Characteristics of tetanic and post-tetanic potentiation in the septohippocampal and hippocampal commissural systems in the acute rabbit

The frequency characteristics of tetanic and post-tetanic potentiation of the septohippocampal and hippocampal commissural systems were studied in the acute rabbit preparation. Glass micropipettes were employed to stimulate the medial septal (MSR) and contralateral CA1 (cCA1) regions. Extracellular postsynaptic potentials were recorded in the stratum radiatum and stratum oriens layers of dorsal CA1. Low frequencies of stimulation (2–12 Hz) and brief stimulus trains (7 or 16 stimuli) ensured that only short-term effects appeared in the data. With MSR and cCA1 stimulation, tetanic potentiation became pronounced at 4 Hz, and plateaued at 6–8 Hz. Thus potentiation was found to be pronounced within the range of the rabbit hippocampal theta rhythm. No differences were found in the characteristics of potentiation evoked by stimulation of MSR and cCA1. Post-tetanic potentiation lasting 6–12 sec was found. Again, potentiation characteristics did not depend on stimulus site, suggesting a common mechanism for the pathways studied. A two-factor mechanism was proposed to account for the post-tetanic potentiation data.     

Cellular mechanisms of paired electrical stimulation in ferret ventricular myocardium: relationship between myocardial force and stimulus interval change

Summary The subcellular mechanisms of twitch-force potentiation with paired electrical stimulation was studied in ferret ventricular myocardium using the bioluminescent calcium indicator aequorin. It is demonstrated for the first time that interpolation of an extrasystole in a train of conditioned twitches results in a beat-to-beat change in [Ca²⁺]_i and force. Steady-state twitch force and Ca _i ²⁺ were increased with paired stimulation. Increased [Ca²⁺]₀ in the setting of paired stimulation resulted in an increase in the amplitude of the postextrasystole and associated Ca²⁺ transient. Verapamil, a Ca²⁺ channel antagonist, had the opposite effect of increased [Ca²⁺]₀. Postextrasystole potentiation was still present, but diminished in amplitude. These results indicate that postextrasystole potentiation is in part due to a verapamil-depletable store (Ca²⁺). Postextrasystole potentiation is therefore predominantly dependent on sarcoplasmic reticulum (SR) Ca²⁺ loading. Ryanodine, an alkaloid which induces Ca²⁺ leakage from the SR, abolished postextrasystole potentiation; however, in the presence of ryanodine the extrasystole was potentiated. Caffeine, a phosphodiesterase inhibitor which induces SR Ca²⁺ release and impairs uptake, also abolished postextrasystole potentiation. As with ryanodine there was resultant potentiation of the extrasystole. In the case of caffeine the calcium transient consisted of a second slow component associated with extrasystole twitch potentiation. The results are consistent with sarcolemmal Ca²⁺ influx playing a role in potentiation of the extrasystole in the presence of an impaired SR. These data indicate that transsarcolemmal Ca²⁺ influx in the presence of impaired intracellular Ca²⁺ buffering can directly activate the myofilaments in agreement with reports on human myocardium.Abbreviations C conditioned stimulus - ESI extrasystolic interval - L_max active tension - PES postextrasystole - PESI postextrasystolic interval - SR sarcoplasmic reticulum - T test stimulus     

The generation of action potentials in the terminals of the Schaffer collaterals during long-term potentiation in the CA1 region of the hippocampus]

Experiments were performed in rat hippocampal slices. Activity of individual CA3 pyramidal neurons and field potentials in the CA1 areas were recorded extracellularly. The collision technique was applied to detect the antidromic origin of the background action potentials in the somata of CA3 neurons. Threshold stimulation of terminals of the Schaffer collaterals in the stratum radiatum of the CA1 area was applied to study their excitability during the CA1 long-term potentiation. During the long-term potentiation, antidromic action potentials appeared in the somata of the CA3 neurons. The obtained evidence suggests that the synaptic potentiation is accompanied by an enhancement of axon terminal excitability resulting in generation of the action potentials.     

Stimulation of the lateral hypothalamus provokes the initiation of robust long-term potentiation of the thalamo-cortical input to the barrel field of the adult, freely moving rat

Long-term potentiation in the thalamo-cortical input to the somatosensory cortex barrel field has been reported to be inducible in vitro only during a narrow critical period of the first postnatal week. Here we explored whether this is due to inability of adult synapses to express LTP or lack of appropriate conditions for LTP induction in slice preparations. We recorded thalamo-cortical field potentials (FPs) from the barrel field of chronically prepared adult rats. In the first series, several parameters of conditioning tetanization of thalamus (T) have been tried. Statistically significant LTP of 135-150% relative to the baseline was observed only in rare cases (3/18) so that the mean changes were not statistically significant. In the second series, five trains of 100 Hz stimulation of T were paired with a "reinforcing" stimulation of the lateral hypothalamus (LH). In most cases (9/13) thalamo-cortical FPs were potentiated. The mean post-tetanic amplitude was 238 +/- 42% (+/- SEM) relative to the baseline (n = 13). The potentiation persisted for > > 1 hr and typically even further increased when tested 24-48 hr later. LTP magnitude strongly correlated with the initial paired-pulse ratio (PPR, coefficient of correlation r = 0.98) so that LTP magnitude was larger (333 +/- 107, n = 6) in cases with PPR > 1.3. The mean PPR tended to decrease after LTP (from 2.05 to 1.65). Altogether the results suggest that LTP is inducible in the thalamo-cortical input to the barrel field of normal adult rats. The dependence of LTP magnitude upon the initial PPR suggests that inputs with low initial release probability undergo larger LTP. Together with the tendency to a decrease in the PPR this suggests an involvement of presynaptic mechanisms in the maintenance of neocortical LTP.     

Evoked potentials in the visual and association cortex of alert cats during paired uniform stimulation of the lateral geniculate body and pulvinar

Recovery curves of evoked potentials in the association and visual cortex during paired stimulation of the pulvinar in chronic experiments on alert cats were shown to be similar in character. Depression of the test response was observed only if the interval between stimuli was of the order of 10 msec, but if it was 40 msec considerable (2–4 times) facilitation of the second response was observed, mainly on account of an increase in the negative component N₁. Facilitation was less marked if the intervals were from 60 to 100 msec, and they decreased gradually to an interval of 200 msec. The recovery curve of cortical evoked potentials during paired stimulation of the lateral geniculate body differed considerably from the recovery curve during paired stimulation of the pulvinar and was characterized by a gradual increase in amplitude of the second response — from its almost total suppression with an interval of 10 msec to slight facilitation with an interval of 200 msec. If intervals of 10 to 80 msec were used, the test response was restored more slowly in the association cortex than in the visual cortex. The results are discussed from the standpoint of differences in the character of intracortical spread of excitation as a result of activation of geniculo-cortical and pulvinar-cortical pathways of conduction of information.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 16, No. 4, pp. 497–505, July–August, 1984.     

Modulation of synaptic plasticity in the hippocampus and piriform cortex by physiologically meaningful olfactory cues in an olfactory association task

Animals were trained to discriminate two natural odors while another group was trained to discriminate between a patterned electrical stimulation distributed on the lateral olfactory tract (LOT), labelled olfaco-mimetic stimulation (OMS), used as an olfactory cue versus a natural odor. No statistically significant difference was observed in behavioral data between these two groups. The animals trained to learn the meaning of the OMS exhibited a gradual long-term potentiation (LTP) phenomenon in the piriform cortex. When a group of naive animals was pseudo-conditioned, giving the OMS for the same number of sessions but without any olfactory training, no LTP was recorded. These results indicate that the process of learning olfactory association gradually potentiates cortical synapses in a defined cortical terminal field, and may explain why LTP in the piriform cortex is not elicited by the patterned stimulation itself, but only in an associative context. As olfactory and hippocampus regions are connected via the lateral entorhinal cortex, the olfactomimetic model was used to study the dynamic of involvement of the dentate gyrus (DG) in learning and memory of this associative olfactory task. Polysynaptic field potentials, evoked by the LOT stimulation, were recorded in the molecular layer of the ipsilateral DG. An early and rapid (2nd session) potentiation was observed when a significant discrimination of the two cues began to be observed. The onset latency of the potentiated response was 30–40 ms. When a group of naive animals was pseudoconditioned, no change was observed. Taken together, these results support the hypothesis that early activation of the DG during the learning of olfactory cue allows the progressive storage of olfactory information in a defined set of potentiated cortical synapses. The onset latency of the polysynaptic potentiated responses suggests the existence of a reactivating hippocampal loops during the processing of olfactory information.     

Effects of adrenal steroids and their reduced metabolites on hippocampal long-term potentiation

We studied the effects of steroid hormones on the hippocampal long-term potentiation (LTP), a putative mechanism of neuronal plasticity and memory storage in the CNS. In vivo experiments were performed in rats under chloral hydrate anesthesia (0.4 mg/kg i.p.). All animals were adrenalectomized 48 h before recording. LTP was induced after priming tetanic stimulation at the perforant pathway (PP) and single pulse field potentials were obtained from the dentate gyrus (DG). The excitatory post-synaptic potential (EPSP) slope and population spike (PS) amplitude were analyzed before and after the i.v. injection of the steroids and after the induction of LTP, and followed up to 1 h. Results obtained with the hormones were compared with matched control animals injected with vehicle alone, Nutralipid 10%. Previous results from our laboratory showed that deoxycorticosterone (DOC) decreased the magnitude of the EPSP at all times after priming stimulation and the PS decreased during the first 30 min of the LTP. Corticosterone decreased the EPSP in the first 15 min and the PS during the first 30 min after priming stimuli. In these experiments the mineralocorticoids aldosterone and 18-OH-DOC elicited a decrease of the EPSP at all times post-train; and no significant difference against vehicle was observed in the PS. Post-injection values were not changed except for 18-OH-DOC at a dose of 1 mg, where a decrease of both the EPSP (P less than 0.01) and the PS (P less than 0.02) was observed against vehicle. ATH-progesterone at 0.1 mg/rat also decreased the EPSP values significantly after priming stimulation and no significant changes against vehicle were observed in the PS. These results show that adrenal steroids can modulate hippocampal LTP, that they can act at different neuronal loci and with different time courses in the development of the phenomena.     

Long-Term Plasticity Is Proportional to Theta-Activity

Background

Theta rhythm in the hippocampal formation is a main feature of exploratory behaviour and is believed to enable the encoding of new spatial information and the modification of synaptic weights. Cyclic changes of dentate gyrus excitability during theta rhythm are related to its function, but whether theta epochs per se are able to alter network properties of dentate gyrus for long time-periods is still poorly understood.

Methodology/Principal Findings

We used low-frequency stimulation protocols that amplify the power of endogenous theta oscillations, in order to estimate the plasticity effect of endogenous theta oscillations on a population level. We found that stimulation-induced augmentation of the theta rhythm is linked to a subsequent increase of neuronal excitability and decrease of the synaptic response. This EPSP-to-Spike uncoupling is related to an increased postsynaptic spiking on the positive phases of theta frequency oscillations. Parallel increase of the field EPSP slope and the population spike occurs only after concurrent pre- and postsynaptic activation. Furthermore, we observed that long-term potentiation (>24 h) occurs in the dentate gyrus of freely behaving adult rats after phasic activity of entorhinal afferents in the theta-frequency range. This plasticity is proportional to the field bursting activity of granule cells during the stimulation, and may comprise a key step in spatial information transfer. Long-term potentiation of the synaptic component occurs only when the afferent stimulus precedes the evoked population burst, and is input-specific.

Conclusions/Significance

Our data confirm the role of the dentate gyrus in filtering information to the subsequent network during the activated state of the hippocampus.