Kindling induces transient fast inhibition in the dentate gyrus--CA3 projection

The granule cells of the dentate gyrus (DG) send a strong glutamatergic projection, the mossy fibre tract, toward the hippocampal CA3 field, where it excites pyramidal cells and neighbouring inhibitory interneurons. Despite their excitatory nature, granule cells contain small amounts of GAD (glutamate decarboxylase), the main synthetic enzyme for the inhibitory transmitter GABA. Chronic temporal lobe epilepsy results in transient upregulation of GAD and GABA in granule cells, giving rise to the speculation that following overexcitation, mossy fibres exert an inhibitory effect by release of GABA. We therefore stimulated the DG and recorded synaptic potentials from CA3 pyramidal cells in brain slices from kindled and control rats. In both preparations, DG stimulation caused excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequences. These potentials could be completely blocked by glutamate receptor antagonists in control rats, while in the kindled rats, a bicuculline-sensitive fast IPSP remained, with an onset latency similar to that of the control EPSP. Interestingly, this IPSP disappeared 1 month after the last seizure. When synaptic responses were evoked by high-frequency stimulation, EPSPs in normal rats readily summate to evoke action potentials. In slices from kindled rats, a summation of IPSPs overrides that of the EPSPs and reduces the probability of evoking action potentials. Our data show for the first time that kindling induces functionally relevant activity-dependent expression of fast inhibition onto pyramidal cells, coming from the DG, that can limit CA3 excitation in a frequency-dependent manner.     

Hyperexcitability of CA3 pyramidal cells in mice lacking the potassium channel subunit Kv1.1

PURPOSE: To investigate further the membrane properties and postsynaptic potentials of the CA3 pyramidal cells in mice that display spontaneous seizures because of a targeted deletion of the Kcna1 potassium channel gene (encoding the Kv1.1 protein subunit). METHODS: Intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices prepared from Kcna1-null and control littermates. CA3 pyramidal cells were activated: orthodromically, by stimulating mossy fibers; antidromically, by activating Schaffer collaterals; and by injecting intracellular pulses of current. Responses evoked under these conditions were compared in both genotypes in normal extracellular medium (containing 3 mM potassium) and in medium containing 6 mM potassium. RESULTS: Recordings from CA3 pyramidal cells in Kcna1-null and littermate control slices showed similar membrane and action-potential properties. However, in 33% of cells studied in Kcna1-null slices bathed in normal extracellular medium, orthodromic stimulation evoked synaptically driven bursts of action potentials that followed a short-latency excitatory postsynaptic potential (EPSP)-inhibitory PSP (IPSP) sequence. Such bursts were not seen in cells from control slices. The short-latency gamma-aminobutyric acid (GABA)A-mediated IPSP event appeared similar in null and control slices. When extracellular potassium was elevated and excitatory synaptic transmission was blocked, antidromic activation or short pulses of intracellular depolarizing current evoked voltage-dependent bursts of action potentials in the majority of cells recorded in Kcna1 null slices, but only single spikes in control slices. CONCLUSIONS: Lack of Kv1.1 potassium channel subunits in CA3 pyramidal cells leads to synaptic hyperexcitability, as reflected in the propensity of these cells to generate multiple action potentials. The action-potential burst did not appear to result from loss of GABAA receptor-mediated inhibition. This property of CA3 neurons, seen particularly when tissue conditions become abnormal (e.g., elevated extracellular potassium), helps to explain the high seizure susceptibility of Kcna1-null mice.     

Convergence of projections from the rat hippocampal formation, medial geniculate and basal forebrain onto single amygdaloid neurons: an in vivo extra- and intracellular electrophysiological study.

We recorded extra- and intracellular responses from rat amygdaloid neurons in vivo after electrical stimulation of the hippocampal formation (dentate gyrus, hippocampal fields CA3 and CA4, entorhinal cortex, subicular complex); medial geniculate; and basal forebrain (diagonal band, ventral pallidum, olfactory tubercle, nucleus accumbens, bed nucleus of stria terminalis, lateral preoptic area, substantia innominata). Stimulation of hippocampal formation structures evoked IPSPs or EPSP-IPSP sequences in which the IPSP had a lower threshold than the EPSP. Recordings from candidate inhibitory neurons in the amygdala indicated that excitatory afferents from the hippocampal formation contact both amygdaloid inhibitory and principal neurons (feedforward inhibition), and that the inhibitory neurons have a lower threshold of activation. Medial geniculate stimulation also evoked EPSP-IPSP sequences. In marked contrast to these results, stimulation of basal forebrain structures evoked short latency IPSPs in amygdaloid neurons. This provides the first physiological evidence for direct inhibition of the amygdala by the basal forebrain. Basal forebrain stimulation also evoked EPSP-IPSP sequences in amygdaloid neurons. Individual amygdaloid neurons could show responses to stimulation of the hippocampal formation, basal forebrain, and medial geniculate, indicating that synaptic input from these areas converges onto single amygdaloid cells. The findings provide further information about the synaptic organization of afferents to the amygdala, and indicate that single amygdaloid neurons play a role in the synaptic integration of input from these diverse sources.     

Epileptiform activity induced by low Mg in cultured rat hippocampal slices

Organotypic cultured slices of the rat hippocampus undergo synaptic reorganization. Besides the establishment of reciprocal connections between area CA1 and the dentate gyrus (DG), collateral excitatory connections between granule cells are formed which are similar to those appearing in several epilepsy models and in the DG from patients with temporal lobe epilepsy. We studied the characteristics of epileptiform activity induced by low Mg²⁺ perfusion in cultured hippocampal slices using extra- and intracellular recordings. With low Mg²⁺ perfusion synchronous seizure like events (SLEs) were readily observed in the DG and areas CA3 and CA1. Also, the isolated DG was able to display seizure like activity. Intracellular recordings revealed long lasting depolarization shifts in granule cells of the DG and pyramidal cells of areas CA3 and CA1. The SLEs, lasting 2–3 s, could be recorded for at least 3 h in areas CA1 and CA3. However, approximately an hour after perfusion with low Mg²⁺, the epileptiform activity disappeared in the DG and responses to single pulse hilar stimulation progressively deteriorated. These responses returned to control values 1 week after reincubating the cultures. Interestingly, no deterioration of stimulus induced responses was observed in the isolated DG after exposure to low Mg²⁺.     

On the sites of presynaptic inhibition by neuropeptide y in rat hippocampus in vitro

Neuropeptide Y (NPY) reduces excitatory synaptic transmission between stratum radiatum and CA1 pyramidal cells in rat hippocampal slice in vitro by a presynaptic action. To understand NPY's role in the control of excitability in hippocampus, its actions on excitatory and inhibitory synaptic transmission were examined, using intracellular, sharp microelectrode, and tight-seal, whole cell recordings from principal neurons in areas CA1, CA3, and dentate. Bath application of 1 μM NPY reversibly inhibited excitatory postsynaptic potentials (EPSPs) evoked in CA1 pyramidal cells from either stratum radiatum or stratum oriens by about 50%. Neuropeptide Y also inhibited EPSPs at mossy fiber-CA3, stratum oriens-CA3, and CA3-CA3 synapses by between 45% and 55%. As in CA1, the action of NPY was presynaptic. By contrast, NPY did not inhibit EPSPs evoked in dentate granule cells from either perforant path or commissural inputs. Neuropeptide Y did not alter postsynaptic membrane properties in any cell type. Although NPY attenuated the orthodromically evoked (stratum radiatum) inhibitory postsynaptic potentials in CA1 pyramidal cells by about the same amount as it inhibited the EPSPs, it did not affect the IPSPs evoked in the same cells by antidromic stimulation from alveus. Inhibitory postsynaptic potentials evoked in pharmacological isolation in CA1, CA3, or dentate were also not significantly affected by NPY. The evidence supports the hypothesis that NPY acts at feedforward excitatory synapses to presynaptically reduce the amplitude of excitation as it travels through hippocampal circuits. By contrast, synaptically mediated inhibition is not directly affected by NPY. Neuropeptide Y is the only known endogenous substance that selectively reduces feedforward excitatory transmission without causing changes in other properties of the hippocampal circuitry.     

Differential effects of pentobarbital and ether on the synaptic transmission of the hippocampal CA1 region in the rat

The effect of ether and sodium pentobarbital on the synaptic transmission of the hippocampal CA1 region was studied in chronically implanted rats. Animal behavior, EEG, and the average evoked potentials (AEPs) following electrical stimulation of the alveus or the stratum radiatum in the CA1 region were recorded. Components of the AEPs, interpreted previously as generated by population excitatory postsynaptic potentials (EPSPs), population inhibitory postsynaptic potentials (IPSPs) (Leung 1979a, b, c) or population postsynaptic spikes (Andersen et al. 1971), were differentially sensitive to ether or pentobarbital. Ether reduced the population EPSPs and population spike evoked at all intensities tested (1-4 X threshold); the population IPSP was slightly enhanced at intermediate stimulus intensities. Pentobarbital suppressed the population EPSP evoked by alvear stimulation but not that by radiatum stimulation, reduced the population spike and greatly enhanced and prolonged the population IPSP evoked at low stimulus intensities. At high stimulus intensities, the IPSP was interpreted to be smaller after pentobarbital but neuronal output from the hippocampal CA1 region, as seen from the evoked population spike, remained attenuated. It is concluded that ether and pentobarbital both suppress hippocampal neuronal excitability but the effect of anesthesia differs for different anesthetics, for different synapses and for different levels of activity in the input fibers.     

Hippocampal kindling induced paired-pulse depression in the dentate gyrus and paired-pulse facilitation in CA3

Rats received high frequency (100 Hz, 1 s) hippocampal stimulations that evoked afterdischarges (ADs) in a partial kindling model of epilepsy. Kindled rats were given 15 ADs over 3 days. Control rats received the same stimulation pulses at 0.17 Hz (low frequency stimulation, LFSs). Subsequent to in vivo stimulations, hippocampal slices were obtained from the rats and extracellular field responses were recorded in the CA3 cell layer following CA1 stratum radiatum stimulation, and in the granule cell layer of the dentate gyrus (DG) following perforant path stimulation. At the DG, the paired-pulse facilitation of the population spike was depressed in the kindled than the control group, on 1 day or 23 days post ADs/LFSs. The excitatory postsynaptic potential (EPSP) responses in DG following single or paired pulses were not different between kindled and control slices. At CA3, paired-pulse facilitation of both the population spike and the population EPSP was increased in the kindled compared to the control group.     

Postischemic synaptic physiology in area CA1 of the gerbil hippocampus studied in vitro

After transient forebrain ischemia in the Mongolian gerbil, CA1b hippocampal pyramidal cells degenerate during a period of 2-4 d. We tested the hypothesis that this delayed neuronal death is preceded by excessive synaptic excitation. Hippocampal slices were prepared from gerbils that had been subjected to a 5 min occlusion of both common carotid arteries. Input/output curves demonstrated enhancement of the initial slope of the Schaffer collateral-commissural focally recorded EPSP at all stimulus currents between 5 and 10 hr after the ischemic insult. The duration of the focally recorded EPSP also increased. At the same time, the excitability of the CA1b pyramidal cells decreased. Thus, the EPSP brought fewer pyramidal cells to threshold than the same size EPSP in control slices. During the first 14 hr after ischemia, the antidromic population spike remained unaffected. By 24 hr after ischemia, however, the focally recorded EPSP and both orthodromic and antidromic population spikes were markedly depressed, and they declined further over the next 2 d. No recovery was detected. In the same slices, transient ischemia only mildly and reversibly affected the response of dentate granule cells to perforant path stimulation and did not affect their response to antidromic stimulation. Hippocampal slices adjacent to those used for electrophysiological recording were analyzed histologically. Examination of somatic argyrophilia confirmed that CA1b pyramidal cells suffered delayed neuronal death, whereas dentate granule cells remained intact. Pyramidal cell argyrophilia was, however, not detected until 2 d after these neurons had become virtually inexcitable. We conclude that CA1b pyramidal cells begin to lose electrophysiological function well before definite morphological signs of degeneration become visible. The observation of enhanced excitatory transmission 5-10 hr after reperfusion is consistent with the idea that delayed ischemic neuronal death results, at least in part, from excessive excitation.     

“Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies

Sustained electrical stimulation of the perforant path in urethane-anesthetized rats evoked hippocampal granule cell population spikes and epileptiform discharges. After stimulation, recurrent inhibition in the granule cell layer was abolished. Light microscopic analysis revealed a highly reproducible pattern of hippocampal damage to dentate pyramidal basket cells, hilar cells in general and CA3 and CA1 pyramidal cells. CA2 pyramidal cells and dentate granule cells were relatively unaffected. When perforant path stimulation on one side of the brain evoked bilateral granule cell discharges, damage was bilateral. Unilateral hippocampal seizures were associated with unilateral hippocampal damage. Rapid Golgi-stained hippocampi exhibited spherical dendritic swellings at the sites of termination of excitatory entorhinal afferents to the hippocampus and in the mossy fiber region. Electrical stimulation of a single excitatory afferent to the hippocampus appears to reproduce the “epileptic” pattern of hippocampal damage without using convulsant drugs and without causing motor convulsions. It is suggested that seizure-associated brain damage in caused by excessive pre-synaptic release of excitatory transmitter that induces intracellular post-synaptic changes that lead to dendritic swelling and cell death.     

Electrophysiology of dentate granule cells after kainate-induced synaptic reorganization of the mossy fibers.

Morphological data from humans with temporal lobe epilepsy and from animal models of epilepsy suggest that seizure-induced damage to dentate hilar neurons causes granule cells to sprout new axon collaterals that innervate other granule cells. This aberrant projection has been suggested to be an anatomical substrate for epileptogenesis. This hypothesis was tested in the present study with intra- and extracellular recordings from granule cells in hippocampal slices removed from rats 1-4 months after kainate treatment. In this animal model, hippocampal cell loss leads to sprouting of mossy fiber axons from the granule cells into the inner molecular layer of the dentate gyrus. Unexpectedly, when slices with mossy fiber sprouting were examined in normal medium, extracellular stimulation of the hilus or perforant path evoked relatively normal responses. However, in the presence of the GABAA-receptor antagonist, bicuculline, low-intensity hilar stimulation evoked delayed bursts of action potentials in about one-quarter of the slices. In one-third of the bicuculline-treated slices with mossy fiber sprouting, spontaneous bursts of synchronous spikes were superimposed on slow negative field potentials. Slices from normal rats or kainate-treated rats without mossy fiber sprouting never showed delayed bursts to weak hilar stimulation or spontaneous bursts in bicuculline. These data suggest that new local excitatory circuits may be suppressed normally, and then emerge functionally when synaptic inhibition is blocked. Therefore, after repeated seizures and excitotoxic damage in the hippocampus, synaptic reorganization of the mossy fibers is consistently associated with normal responses; however, in some preparations, the mossy fibers may form functional recurrent excitatory connections, but synaptic inhibition appears to mask these potentially epileptogenic alterations.     

Effect of early isolation on the synaptic function in the dentate gyrus and field CA1 of the guinea pig

We previously reported that neonatal isolation shapes neuron morphology remarkably in the dentate gyrus and hippocampus of the guinea pig, a precocial rodent whose brain is at an advanced stage of maturation at birth. The aim of the present work was to investigate the effects of early isolation on the physiology of the hippocampal trisynaptic circuit. Male and female guinea pigs were assigned at 6-7 days of age to either a social or an isolated environment. After 90-100 days, the animals were anesthetized and electrophysiological experiments were carried out. The monosynaptic response evoked by medial perforant path stimulation in the dentate gyrus (DG) and the following response trisynaptically evoked in field CA1 by the DG-CA3 system were evaluated with several stimulus protocols: (1) current source-density (CSD) analysis; (2) input/output function; (3) paired-pulse potentiation (PPP); and (4) long-term potentiation (LTP). Isolated animals exhibited a reduction in the magnitude of the current sinks in the middle molecular layer and granule cell layer of the DG and in the input/output function of the granule cell population excitatory postsynaptic potential (EPSP) and population spike (PS) over a wide range of stimuli. The latter effect was larger in males. The ratio between the PS and EPSP of the granule cells was reduced in isolated compared to control males, but the opposite occurred in females. Isolation affected PPP of the granule cell response in males only, causing a larger facilitation of the PS. No isolation-related effects were found in the magnitude of the LTP of the DG response in either sex. Isolated animals exhibited a reduction in the current sinks in stratum radiatum and stratum pyramidale of field CA1 and in the input/output function of the EPSP and PS of field CA1. These effects were larger in males. The results show that early isolation causes a reduction in the synaptic function of the DG-CA3-CA1 system, driven by perforant path volleys. The isolation-induced impairment in signal processing along the hippocampal network suggests that the outcome of early isolation may be an impairment in the memory functions in which the entorhinal-hippocampal system plays a key role.     

Contribution of T-type VDCC to TEA-induced long-term synaptic modification in hippocampal CA1 and dentate gyrus

We have previously reported that exposure to the K+ channel blocker tetraethylammonium (TEA), 25 mM, induces long-term potentiation (LTP) in CA1, but not in the dentate gyrus (DG), of the rat hippocampal slice. During TEA application, stimulation of excitatory afferents results in a strong depolarizing potential after the fast excitatory postsynaptic potential (EPSP) in CA1, but not in DG. We hypothesized that the differential effect of TEA on long-term synaptic modification in CA1 and DG results from different levels of TEA-elicited depolarization in the two cell types. Additional pharmacological studies showed that blockade of T-type voltage-dependent calcium channels (VDCCs) decreased both the magnitude of LTP and the late, depolarizing potential in CA1. Blockade of L-type VDCCs had no such effect. Using computer models of morphologically reconstructed CA1 pyramidal cells and DG granule cells, we tested our hypothesis by simulating the relative intracellular Ca2+ accumulation and membrane potential changes mediated by T-type and L-type VDCCs. Simulation results using pyramidal cell models showed that, with decreased maximum conductance of TEA-sensitive potassium channels, synaptic inputs elicited strong depolarizing potentials similar to those observed with intracellular recording. During this depolarization, VDCCs were opened and resulted in a large intracellular Ca2+ accumulation that presumably caused LTP. When T-type VDCCs were blocked, the magnitudes of both the Ca2+ accumulation and the late depolarizing potential were decreased substantially. Simulated blockade of L-type VDCCs had only a minor effect. Together, our modeling and experimental studies indicate that T-type VDCCs, rather than L-type VDCCs, are primarily responsible for facilitating the depolarizing potential caused by TEA and for the consequent Ca2+ influx. Thus, our findings strongly suggest that the induction of TEA-LTP in CA1 depends primarily on T-type, rather than L-type, VDCCs. Simulation results using modeled granule cells suggests that the failure of TEA to induce LTP in DG is partly due to a low density of T-type VDCCs in granule cell membranes.     

Activation of identified septo-hippocampal neurons by noxious peripheral stimulation

In vivo intracellular recordings were obtained from septohippocampal neurons identified by their antidromic response to electrical stimulation of the fimbria in rats anesthetized with pentobarbital or urethane. Beside the antidromic response, fimbria stimulation evoked a short-latency depolarizing potential (EPSP) followed by an hyperpolarizing potential which reversed polarity when recorded with KCl-filled electrodes. This IPSP is therefore likely to be chloride-dependent. It was followed by a long-lasting (80-250 ms) depolarizing potential often associated with a burst of spikes. Septohippocampal neurons therefore receive an inhibitory, chloride-mediated, input which itself triggers a long-lasting excitatory event. These results are consistent with extracellular observations. Their significance in the septohippocampal circuitry is discussed.     

单侧液压脑损伤对大鼠双侧海马GFAP表达和CA1区突触传递的影响

目的研究单侧液压脑损伤(FPI)对大鼠双侧海马区胶质纤维酸性蛋白(GFAP)表达和CA1区突触传递的影响。方法建立大鼠单侧液压脑损伤模型,脑标本分为对照组(包括正常对照和假手术对照)、FPI损伤同侧组和FPI损伤对侧组。免疫组化法检测海马水平切片GFAP表达,对海马CA1区锥体神经元进行细胞内记录。结果FPI大鼠双侧海马齿状回门区和CA1区GFAP表达均比对照组明显增强。FPI损伤同侧组兴奋性输入-输出关系曲线的斜率比其他两组显著增大(P<0.05);FPI损伤同侧组和对侧组双脉冲易化(PPF)比值和抑制性突触后电位(IPSP)幅值均比对照组显著减小(P<0.05);FPI损伤同侧组和对侧组双脉冲抑制(PPD)比值均比对照组显著增大(P<0.05)。结论大鼠单侧液压脑损伤对双侧海马均可产生影响,导致双侧海马CA1区兴奋性突触传递增强,抑制性突触传递减弱。     

Norepinephrine decreases synaptic inhibition in the rat hippocampus

The effects of norepinephrine (NE) on inhibitory synaptic potentials were studied on CA1 pyramidal neurons in the hippocampal slice in vitro. Norepinephrine caused the appearance of multiple population spikes in the CA1 region of the hippocampal slice, reminiscent of the actions of gamma-aminobutyric acid (GABA) antagonists. Intracellular recording revealed that NE causes a marked and reversible reduction in inhibitory postsynaptic potentials (IPSPs) recorded in CA1 pyramidal cells. This reduced IPSP results in a larger intracellular excitatory postsynaptic potential (EPSP), which can cause the cell to fire more than one action potential. This disinhibitory effect of NE appears to be mediated by an alpha-receptor, and occurs at a site presynaptic to the pyramidal cell, since NE does not change the reversal potential of the IPSP nor does it affect the amplitude or the reversal potential of iontophoretic GABA responses. In addition to reducing evoked IPSPs, NE causes an increase in the frequency of spontaneous IPSPs, suggesting that inhibition of interneuronal firing may not account for this disinhibitory action of NE.     

Conductance changes and inhibitory actions of hippocampal recurrent IPSPs

Intracellular recordings were obtained from CA1 pyramidal neurons in obliquely cut in vitro hippocampal slices. Recurrent IPSPs were elicited by antidromic stimulation of alvear fibers. The mechanisms by which IPSPs depress pyramidal cell excitability were investigated.Recurrent IPSPs could be reversed in sign by small hyperpolarizing currents applied through the recording electrode, indicating an increased membrane conductance. By using an AC bridge circuit it was found that the maximum impedance decrease usually occurred slightly before the peak of the IPSP. Otherwise the time course of the impedance change matched that of the IPSP itself.Inhibitory actions of the conductance increase were studied by adjusting the membrane potential to the IPSP equilibrium potential, thus allowing only the IPSP conductance to play an inhibitory role. Under these conditions non-linear summation of recurrent IPSPs with EPSPs originating in the apical dendrites could be demonstrated only during the initial 15–25 msec of the IPSP, which is the period of maximum conductance increase.The inhibition afforded by the hyperpolarization of the recurrent IPSP far outlasts the period of effective EPSP shunting by the inhibitory synaptic currents. The mechanisms of recurrent inhibition in the hippocampus thus appear similar to those operating in spinal motoneuron IPSPs.     

Kindling with stimulation of the dentate gyrus. II. Effects on evoked field potentials

Once daily for 60 days, male hooded rats received unilateral high-frequency stimulation in the hilus of the dentate gyrus (DG), at an intensity sufficient to evoke afterdischarge (AD). Every 2nd day, evoked potentials were recorded from the hilus following stimulation of the PP with single 0.1 ms pulses at 6 current intensities. Changes in synaptic excitability of the dentate granule cells were monitored by measuring the amplitudes of the population spikes; changes in the strength of excitatory synaptic transmission were monitored by measuring the slopes of the excitatory postsynaptic potentials (EPSPs). Control rats, which were not given kindling stimulation, were tested for changes in synaptic transmission and excitability in the same way, at comparable times. In general, hilar stimulation resulted in a large decrease in population spike amplitudes to below baseline and control levels, accompanied by a paradoxical potentiation of EPSPs. Population spike amplitudes decreased more in rats that developed generalized stage-5 seizures (Generalized group) than in rats that did not progress beyond partial seizures despite 60 days of stimulation (Partial group). Conversely, EPSP slopes increased more in the Partial group than in the Generalized group. These results suggest that kindling stimulation may potentiate responsiveness of the directly activated dentate granule cells to inputs from the PP, but at the same time suppress the output of the granule cells resulting from this input. Furthermore, the results indicate that kindling is more closely allied to the suppression of output than to the potentiation of responsiveness to input.     

Induction and transient suppression of long-term potentiation in the peri- and postrhinal cortices following theta-related stimulation of hippocampal field CA1

During behavioral events associated with periods of likely mnemonic processing, CA1 pyramidal cells in rats typically discharge repetitively in either high-frequency bursts (`complex spikes') or single spikes, both of which are tightly phase-locked to the hippocampal theta rhythm. Interestingly, patterned stimulation which mimics the repetitive, learning-related complex spike discharges are optimal for inducing long-term potentiation (LTP) of excitatory field potentials in CA1, and patterned stimulation which mimics the theta-related single action potentials results in a robust and lasting depotentiation at these same synapses. The aim of the present study was to determine the extent to which these physiologically-relevant patterns of hippocampal stimulation have similar effects on synaptic efficacy in the monosynaptic projection from CA1 to the perirhinal and postrhinal cortices (PRh), areas thought to play a prominent role in many forms of learning and memory. Single-pulse stimulation of CA1 evoked a small amplitude, short latency population excitatory postsynaptic potential (EPSP) in the PRh. Theta-burst stimulation (TBS; n=8) delivered to CA1 reliably potentiated the PRh EPSP slope for at least 30 min. Theta-pulse stimulation (TPS; 5 Hz; n=4) delivered to CA1 5 min after TBS substantially but transiently suppressed EPSP slope relative to that of potentiated control preparations. Collectively these data suggest that theta-related patterns of hippocampal activation can reliably induce and transiently suppress LTP in PRh, and are consistent with the notion that behaviorally-relevant, theta-modulated patterns of CA1 unit activity may result in both long- and short-term alterations of synaptic strength within their rhinal cortical targets.     

An olfactory input to the hippocampus of the cat: Field potential analysis

Hippocampal responses to electrical stimulation of the prepyriform cortex in the cat were studied both in acute experiments under halothane anesthesia and in awake cats with chronically indwelling electrodes. Analysis of field potentials and unit activity indicated the extent to which different hippocampal subareas were activated, the laminar level at which the synaptic action took place and the dynamics of the evoked responses. It was found that: (1) the main generator of evoked responses in the hippocampus upon prepyriform cortex stimulation is localized in the fascia dentata and CA3 (CA1 pyramidal cells, and probably also subiculum cells, are activated but in a lesser degree); (2) the initial synaptic activity takes place at the most distal part of the dendrites of fascia dentata granule cells and CA3 pyramidal cells; and (3) this synaptic activity corresponds to an EPSP that leads to a transient increase in the firing rate of the hippocampal units, which is often followed by a long-lasting decrease in firing rate.We conclude that the pathway from the prepyriform cortex via lateral entorhinal cortex to hippocampal neurons may enable olfactory inputs to effectively excite hippocampal neurons.     

Chelation of postsynaptic Ca2+ facilitates long-term potentiation of hippocampal IPSPs.

In guinea pig hippocampal slices, a tetanic stimulation of the stratum radiatum caused long-term potentiation (LTP) of the excitatory postsynaptic potential (EPSP) but not of the GABAB receptor-mediated slow inhibitory postsynaptic potential (IPSP) in the CA1 neurons. In neurons in which Ca2+ was chelated with 1,2-bis(2-aminophenoxy) ethane N,N,N',N'-tetra-acetic acid (BAPTA) or ethylene-bis(oxyethylenenitrilo)tetra-acetic acid (EGTA), tetanic stimulation of the stratum radiatum caused LTP of the slow IPSP but not of the EPSP. These results indicate that a reciprocal relationship exists between LTP of the EPSP and LTP of the slow IPSP as far as the involvement of the postsynaptic Ca2+ is concerned.