Population Excitatory Postsynaptic Potential Research Articles

Effects of a cAMP analogue simulate the distinct components of long-term potentiation in CA 1 region of rat hippocampus

Bath application of the cAMP analogue, dibutyryl cyclic adenosine 3′,5′-monophosphate (dibutyryl cyclic AMP; dbcAMP) to rat hippocampal slices was found to potentiate both the CAI population spike and population excitatory post-synaptic potential (EPSP) slope. dbcAMP (500–1000 μM) was applied to slices for 30 min; following washout the population EPSP slope was potentiated for at least 30 min to a mean value of 51% above the drug-free baseline value. The population spike was similarly potentiated to a mean value of 64% above baseline after dbcAMP washout. dbcAMP-induced population EPSP slope potentiation occluded long-term potentiation (LTP) induced by high frequency electrical stimulation, and UP occluded dbcAMP-induced EPSP slope potentiation. Earlier investigations (Pockett et al., Neuroscience, 52 (1993) 229–236) using 200 μM dbcAMP reported similar potentiation of population spike but no potentiation of EPSP slope. These experiments support the hypothesis that the two components of UP (Bliss and Lynch, In P.W. Landfield and S.A. Deadwyler (Eds.), Long-term Potentiation: from Biophysics to Behaviour, Alan R. Liss, New York, 1988, pp. 3–72) in the CAI area of rat hippocampus both involve distinct cAMP-dependent mechanisms.

Age-dependent inhibition of long-term potentiation by ethanol in immature versus mature hippocampus.

The goal of this study was to assess the effects of ethanol on the induction of long-term potentiation (LTP) in hippocampal slices from immature versus mature rats. Population excitatory postsynaptic potentials (pEPSPs) were recorded from stratum radiatum of area CA1 of hippocampal slices using electrical stimulation of the Schaffer collateral/commissural fiber pathway. The slices were prepared from rats aged 15 to 25 or from 70 to 100 days. Long-term potentiation (LTP) of the pEPSP slope was induced using a single, theta-burst stimulus train in the presence or absence of 60 mM ethanol. Under control conditions, the stimulus train induced LTP in slices from both immature and mature animals. However, the magnitude of LTP was greater in slices from immature rats. When ethanol was present during the stimulus train, the magnitude of LTP in slices from mature animals did not differ significantly from the magnitude of LTP in control slices. However, ethanol virtually blocked the induction of LTP in slices from immature animals. These results indicate that memory-related synaptic plasticity in the hippocampus is attenuated by ethanol to a greater degree in immature versus mature animals.

The azapirone metabolite 1-(2-pyrimidinyl)piperazine depresses excitatory synaptic transmission in the hippocampus of the alert rat via 5-HT 1A receptors

The effects of acute and repeated treatment with 1-(2-pyrimidinyl)piperazine (1-PP), a metabolite of the 5-HT 1A receptor ligand azapirones, were investigated on hippocampal excitatory synaptic transmission. Recordings of the electrically evoked field population excitatory post-synaptic potentials (e.p.s.p.s) were carried out in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert rats. Acute i.p. administration of 1-PP transiently reduced the e.p.s.p. amplitude in a dose-dependent (0.25–1 mg/kg) manner. This effect was blocked by the 5-HT 1A receptor antagonists spiroxatrine (1 mg/kg) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl methylaminoethyl]-8-azaspirol[4,5]decane-7,9-dione methyl sulphonate, 2 mg/kg). Intraphippocampal administration of 1-PP (5 μg) evoked a transient reduction of the e.p.s.p. amplitude which was similar to that obtained with 5-HT (10 μg). 1-PP (0.25 mg/kg per day) administered for 9 days produced a gradual reduction in the daily pre-injection baseline e.p.s.p. amplitude coupled with a decrease in the acute response to the drug. The chronic baseline reduction was transiently reversed by spiroxatrine and full recovery to pretreatment levels was observed 4 days after the last 1-PP dose. These findings indicate that the previously reported reduction in the e.p.s.p. produced by the azapirone group of 5-HT 1A receptor ligands may be mediated in part by their metabolite 1-PP through activation of 5-HT 1A receptors.

The anticonvulsant gabapentin enhances promoted release of GABA in hippocampus: a field potential analysis

The mechanism of action of the recently developed anticonvulsant gabapentin (GBP) used for treatment of partial seizures [12] is largely unknown. Rat hippocampal slices were maintained in vitro and the effects of microapplication of nipecotic acid (NPA), which promotes the release and blocks uptake of GABA, on the synaptically-evoked population excitatory postsynaptic potential (EPSP) were assessed before and after 1 h bath application of GBP. GBP treatment did not alter the population EPSP amplitude to paired or multiple stimuli, but nearly doubled the shunting effects of NPA on the EPSP with no effect on the presynaptic volley. The NPA-induced shunting of the EPSP was bicuculline-sensitive, indicating its mediation by GABA A receptor activation. These results suggest that GBP may increase free GABA levels in hippocampal cells, the release of which may be enhanced under conditions of promoted GABA release. Moreover, the study presents a methodology to electrophysiologically assess relative free GABA levels using field potential analysis in the adult rat brain.

Long-term potentiation in vivo in the intact mouse hippocampus

We describe the characteristics of long-term potentiation (LTP) in the intact mouse. Perforant path stimulation evokes both a population excitatory postsynaptic potential (pop-EPSP) and a population spike potential (pop-spike) from the hippocampal dentate gyrus in urethane anesthetized animals. LTP, as measured by increased pop-spike amplitude and pop-EPSP slope, was successfully induced and reliably maintained at a stable level for at least 12 h, the longest time tested. The LTP-inducing stimulus (3 trains of 400 Hz, 8 0.4 ms pulses/train) used in two strains of mice was less by half than that used in rat. These parameters for inducing LTP were also successfully applied to obtain LTP in two different transgenic mouse strains: one bearing a F1/GAP-43 promoter-lacZ fusion gene and another which overexpresses the S100β gene. We also examined the effects of protein synthesis inhibitors, cycloheximide (CXM) and anisomycin (ANI). When CXM or ANI was given 30 min before LTP induction, there was no persistent loss of LTP at the 4 h time point. However, if CXM was given 4 h before LTP induction, significant decay of the potentiated responses occurred 90 min after induction. Half of the animals receiving CXM but not ANI showed a complete and sudden elimination of the entire response after the LTP-inducing stimulus. It was speculated that loss of a constitutively-expressed housekeeping protein, for example a calcium buffering protein, with an estimated half-life of 2 h would lead to an inability to buffer LTP-induced alterations, such as intracellular calcium elevation, increasing intracellular calcium to toxic levels. LTP can be reliably studied in the intact mouse hippocampus and can be usefully applied in both wild-type and transgenic preparations. It will afford the opportunity to study LTP in mouse mutants in their in vivo state rather than in vitro in the slice preparation permitting characterization of biochemical and molecular events after LTP and then to determine the explicit relation of these events with the physiology of synaptic enhancement.

Simultaneous expression of excitatory postsynaptic potential/spike potentiation and excitatory postsynaptic potential/spike depression in the hippocampus.

Tetanic stimulation of afferents in the stratum radiatum of the CA1 area of the rat hippocampus results in long-term potentiation of excitatory synaptic responses in pyramidal cells. Previous studies have reported a greater increase in the population spike amplitude following the induction of long-term potentiation than could be accounted for by the increase of the slope of the population excitatory postsynaptic potential. Two hypotheses have been proposed to explain this phenomenon (called excitatory postsynaptic potential/spike potentiation): a modification of the firing threshold and/or a modification of the inhibitory drive. Previous studies have not, however, addressed the question of possible changes in spike threshold in association with long-term depression. This paper examines whether the concomitant long-term potentiation of pharmacologically isolated N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potentials, reported previously, is also associated with a change in spike threshold. When the amplitude of the population spike is plotted as a function of the slope of the population excitatory postsynaptic potential (excitatory postsynaptic potential/spike curve), excitatory postsynaptic potential/spike potentiation (depression) is seen as a shift of the excitatory postsynaptic potential/spike curve to the left (right) following a conditioning stimulus. In this study, using kainic acid lesioned hippocampus, we have shown that tetanic stimulation produced excitatory postsynaptic potential/spike potentiation of the control synaptic response and excitatory postsynaptic potential/spike depression of the isolated N-methyl-D-aspartate receptor-mediated responses.

Simultaneous expression of long-term depression of NMDA and long-term potentiation of AMPA receptor-mediated synaptic responses in the CA1 area of the kainic acid-lesioned hippocampus.

This study investigates the plasticity of the excitatory synapses in an experimental model of epilepsy, the kainic acid-lesioned rat hippocampus. Stimulation of afferents in the CA1 area of lesioned hippocampi produced an epileptiform burst of action potentials, with an underlying synaptic potential composed of mixed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA; 80%) and N-methyl-D-aspartate (NMDA; 20%) receptor-mediated components. Tetanic stimulation yielded a long-term potentiation (LTP) of the mixed AMPA/NMDA receptor-mediated population excitatory postsynaptic potentials. However, the same type of tetanus resulted in a long-term depression (LTD) of pharmacologically isolated NMDA receptor-mediated responses. This LTD occurred independently of the antagonism of AMPA receptors. This suggests that tetanic stimulation produced LTP of AMPA and LTD of NMDA receptor-mediated responses simultaneously. Finally, both LTP and LTD were shown to be NMDA dependent. This property has profound functional implications for the control of excitatory networks in temporal lobe epilepsy.

GABA B receptors modulate synaptically-evoked responses in the rat dentate gyrus, in vivo

We assessed the effects of systemically injected baclofen, a GABA B agonist, on single and paired-pulse responses in the dentate gyrus of urethane-anesthetized rats, in vivo. Baclofen (10 mg/kg) significantly increased the duration of single excitatory responses. This increase was blocked by the GABA B receptor antagonist, CGP 35348, indicating that baclofen was acting through GABA B receptors. To determine the mechanism underlying this increase in response duration, the NMDA antagonist, d-2-amino-5-phosphonopentanoic acid ( d-APV), was administered intracerebroventricularly (i.c.v.) after baclofen. d-APV by itself had no effect on the duration of the population excitatory post-synaptic potential (EPSP). However, when infused after baclofen, d-APV blocked the baclofen induced increase in EPSP duration. This indicates the prolonged EPSP duration caused by baclofen resulted from an enhancement of an NMDA receptor mediated component of the response. We then examined the effect of baclofen on population responses to paired stimuli. Baclofen attenuated paired-pulse inhibition of population spike amplitudes at a 25 ms interstimulus interval. CGP-35348 reduced the effect of baclofen on paired-pulse inhibition, indicating that baclofen suppressed paired-pulse inhibition by acting on GABA B receptors. In contrast to its disinhibitory effect at the 25 ms interval, baclofen had an inhibitory effect on responses evoked at a 150 ms interstimulus interval. Under control conditions, we observed that when stimuli were delivered 150 ms apart, both the EPSP duration and population spike amplitude evoked by the second stimulus were enhanced. Baclofen suppressed this enhancement. We conclude that GABA B receptor activation by baclofen reduces short interval inhibition and this reduction of inhibition leads to an enhanced NMDA-receptor mediated response. We also conclude that by reducing inhibition, baclofen occludes paired-pulse disinhibition found at longer interstimulus intervals. In contrast, CGP-35348 directly blocks paired-pulse disinhibition. Thus, GABA B receptor activation can regulate synaptic inhibition, in turn influencing NMDA receptor activation and synaptic transmission. Thus, pharmacologic manipulation of GABA B receptors may provide a powerful approach for regulating synaptic transmission in the hippocampus.

Cholinergic manipulations in the medial septal area: age-related effects on working memory and hippocampal electrophysiology

Aged rats have impairments in several types of cognitive functions, including spatial working memory (WM), that are dependent upon the septohippocampal cholinergic system. The present series of experiments was designed to assess the effectiveness of pharmacological manipulations of the medial septal area (MSA) in order to influence the physiology of the septohippocampal pathway and, therefore, the brain functions in which this pathway participates. Aged (22MO) and young (4MO) Fischer-344 rats received microinfusions into the MSA with either saline, the muscarinic agonist, oxotremorine (OXO), or the muscarinic antagonist, scopolamine (SCOP). Working memory was tested in a T-maze spatial alternation task, prior to infusion, immediately after infusion, and 90 min after infusion. Hippocampal theta activity and the population excitatory postsynaptic potential (pEPSP) of the dentate gyrus to perforant path stimulation were recorded immediately following behavioral testing at each of the three time periods. In 22MO rats, intraseptal OXO (0.5 micrograms, 2 micrograms, 5 micrograms) produced a dose-dependent improvement in choice accuracy, a shift of the hippocampal theta peak to a lower frequency and a higher peak power, and an increase in the initial slope of pEPSP. OXO, 0.1 microgram, did not have an effect on behavior or hippocampal physiology and OXO, 10 micrograms, produced an impairment in performance. In 4MO rats, OXO did not affect choice accuracy, nor the pEPSP slope, but altered hippocampal theta peak frequency and power similarly as in 22MO. The lowest behaviorally effective dose, 0.5 microgram OXO, did not influence WM performance when infused into the lateral ventricles (intracerebroventricularly) of either 22MO or 4MO rats. SCOP (2 micrograms, 5 micrograms, 15 micrograms) decreased choice accuracy in a dose-dependent fashion in both 22MO and 4MO rats. However, in 22MO rats, the behavioral dose-response curve for scopolamine was shifted towards greater sensitivity. SCOP produced a shift of the hippocampal theta to a higher frequency and a lower peak power, and a decrease in the initial slope of pEPSP. In 4MO rats, SCOP altered hippocampal theta similarly to 22MO, but did not affect the pEPSP slope. These results indicate that (1) cholinergic receptors in the MSA are a useful target for drugs to improve WM in aging rats, (2) age-related changes in the activity of the septohippocampal pathway may increase its sensitivity to drugs which alter its activity, and (3) alterations in hippocampal physiology may contribute differently to changes in WM in young and in old rats.

Metabotropic glutamate receptor-mediated presynaptic depression at corticostriatal synapses involves mGLuR2 or 3

1. The pharmacology of the metabotropic glutamate receptor (mGluR) that mediates synaptic depression at corticostriatal synapses was investigated with the use of field potential and whole cell patch-clamp recording from striatal slices and whole cell recordings from isolated striatal neurons. 2. The mGluR2,3-selective agonists (R,S)-4-carboxy-3-hydroxyphenylglycine (CHPG), (2S, 1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV), and (2S, 3S, 4S)-alpha-(carboxycyclopropyl) glycine (L-CCG-I) inhibited the synaptically driven population spike (PS) evoked by afferent stimulation during field potential recording in striatal slices. These agonists also inhibited excitatory postsynaptic potentials (EPSPs) evoked by afferent stimulation during whole cell recordings. The metabotropic receptor antagonist R,S-alpha-methyl-4-carboxyphenylglycine (MCPG) blocked the synaptic depressant actions of DCG-IV and trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD). 3. The mGluR4,6,7-selective agonist L-serine-O-phosphate (L-SOP) did not alter corticostriatal synaptic transmission, but both this agonist and the mGluR4,6,7 agonist D,L-2-amino-4-phosphonobutyric acid (AP4) reduced the amplitude of the population EPSP and PS evoked in the dentate gyrus (DG) by stimulation of the lateral perforant path (LPP). These data are consistent with earlier observations that AP4 does not inhibit corticostriatal transmission, but produces presynaptic depression at LPP-DG synapses. 4. Application of mGluR agonists that inhibited transmission did not alter the input resistance or excitability of striatal neurons and did not inhibit responses evoked by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous potentiation of focal potentials of the CA1 field in long-surviving hippocampal slices of the rat in the absence of electrical stimulation.

The changes in the efficiency of the synaptic transmission in the Schaffer collaterals-field CA1 neurons pathways following prolonged deprivation of afferentation, the cessation (up to four hours) of stimulation of the tested input with brief series of tests every hour (the control afferent inputs, were stimulated throughout the entire experiment at a frequency of 0.05/sec), were investigated in surviving slices of the hippocampus of rats. The evoked focal potentials, population spikes (PS) and population excitatory postsynaptic potentials (pEPSP) were recorded. The prolonged cessation of stimulation led to a significant (p < 0.001) increase in the amplitude of the PS (up to 208% in relation to the baseline level). This phenomenon of potentiation was specific in relation to input and exhibited the properties of "E-S potentiation". A hypothesis is advanced regarding the association of mechanisms responsible for the development of "deprivational" potentiation and of the late phase of long-term posttetanic potentiation.

Acute tolerance to the excitatory effects of opioids in the rat hippocampus.

Prolonged iontophoretic administrations of delta- and mu-selective opioid receptor agonists were conducted in the hippocampus of rats, in order to study the possible development of acute tolerance to the excitatory effects of the opioids. Acute tolerance (AT) to the excitatory effects of the delta-selective opioid receptor agonist Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET) was observed when the drug was applied locally for 3-5 min in the CA1 hippocampal pyramidal neurons. The acute tolerance was expressed as a decrease in the commissurally evoked spike responsiveness during peptide's administration and led to a long-lasting potentiation of the population spike (PS) upon its withdrawal. In all cases, where AT and spike potentiation were evident, the population excitatory postsynaptic potential (pEPSP) remained unaltered. Pharmacological studies of AT and long-lasting spike potentiation showed the following: (1) the nonselective opioid receptor antagonist, naloxone, while effective in blocking the excitatory effects of DSLET when applied prior and during the application of the latter, failed to exhibit any effect on the long-lasting potentiating effect of the opioid; and (2) during the spike potentiation phase, administration of DSLET exhibited a depressant effect towards baseline values. This depressant effect of the opioid was evident 2-3 min from the beginning of the application and was completely antagonized by naloxone. The above results show that the development of acute tolerance to the excitatory effects of the DSLET led to long-lasting spike potentiation, which manifests a withdrawal phenomenon.

Input-output relations in the entorhinal-hippocampal-entorhinal loop: entorhinal cortex and dentate gyrus.

The pattern of impulse transfer along the entorhinal-hippocampal-entorhinal loop has been analyzed in the guinea pig by field potential analysis. The loop was driven by impulse volleys conducted by presubicular commissural fibers, directly stimulated in the dorsal psalterium, which monosynaptically activated perforant path neurons in the medial entorhinal cortex. Perforant path volleys activated in sequence the dentate gyrus, field CA3, field CA1, subiculum, and entorhinal cortex. Input-output curves were reconstructed from responses simultaneously recorded from different stations along the loop. The entorhinal response to the presubicular volley was found to increase gradually with respect to its input. The population excitatory postsynaptic potential (EPSP) of the dentate gyrus granule cells had a similar behavior. By contrast, the input-output relation between the granule cell population spike and population EPSP was described by a very sleep sigmoid curve. The population spike of CA3 and CA1 pyramidal neurons as well as the response evoked in the entorhinal cortex by the hippocampal output had slightly higher threshold than the granule cell population spike and, like the latter, abruptly reached maximum amplitude. These findings show that the entorhinal-hippocampal-entorhinal loop transforms a linear input in a non-linear, almost all-or-none output and that the dentate gyrus is the critical site where the transformation occurs. Beyond the dentate gyrus, the loop appears very permeant to impulse traffic.

Dehydroepiandrosterone sulfate suppresses hippocampal recurrent inhibition and synchronizes neuronal activity to theta rhythm.

Several neurosteroids have proconvulsant and memory-enhancing properties and are potent modulators of the gamma-amino butyric acid (GABA) receptor/chloride-ionophore complex. The effects of in situ microelectrophoretic application of the natural sulfate ester of the neurosteroid dehydroepiandrosterone (DHEAS) on evoked field responses and single-unit activity were evaluated in the dentate gyrus and CA1 hippocampal subfield of halothane-anesthetized rats. The effects of endogenous stimulation of DHEAS by in situ micropressure application of Trilostane ((4 alpha, 5 alpha, 17 beta)-4,5-epoxy-3,17-dihydroxyandrost-2-ene-2- carbonitrile (WIN24540)), an inhibitor of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), the enzyme that metabolizes DHEAS, on evoked responses and cellular activity in the hippocampus were also investigated. In situ microelectrophoretic application of DHEAS or micropressure application of Trilostane into CA1 markedly increased population excitatory postsynaptic potential (pEPSP) slopes and population spike (PS) amplitudes. Neither DHEAS nor Trilostane altered dentate pEPSP slopes or PS amplitudes, but both increased the amplitude of a late component of the pEPSP. Both DHEAS and Trilostane abolished GABA-mediated paired-pulse inhibition in both the dentate and CA1. In addition, both DHEAS and Trilostane markedly increased the spontaneous firing rate of dentate hilar interneurons (INTs: 256% and 185%), CA1 pyramidal cells (PCs: 95% and 105%), and CA1 oriens/alveus (O/A) interneurons (179% and 85%) and synchronized their firing to hippocampal theta rhythm induced by tail-pinch. These findings indicate that exogenous application and endogenous stimulation of DHEAS modulates hippocampal GABA inhibition in a physiologically relevant manner possibly by entraining hippocampal neurons to theta rhythm.

Long-term potentiation deficits and excitability changes following traumatic brain injury

The effects of traumatic brain injury (TBI) on hippocampal long-term potentiation (LTP) and cellular excitability were assessed at postinjury days 2, 7, and 15. TBI was induced using a well-characterized central fluid-percussion model. LTP of the Schaffer collateral/commissural system was assessed in vivo in urethane-anesthetized rats. Significant LTP of the population excitatory postsynaptic potential (EPSP) slope was found only in controls, and no recovery to control levels was observed for any postinjury time point. Four measurement parameters reflecting pyramidal cell discharges (population spike) indicated that TBI significantly increased cellular excitability at postinjury day 2: (1) pretetanus baseline recording showed that TBI reduced population spike threshold and latency; (2) tetanic stimulation (400 Hz) increased population spike amplitudes to a greater degree in injured animals than in control animals; (3) tetanus-induced population spike latency shifts were greater in injured cases; and (4) tetanic stimulation elevated EPSP to spike ratios (E-S potentiation) to a greater degree in injured animals. These parameters returned to control levels, as measured on postinjury days 7 and 15. These results suggest that TBI-induced excitability changes persist at least through 2 days postinjury and involve a differential impairment of mechanisms subserving LTP of synaptic efficacy and mechanisms related to action potential generation.

Zinc induces hyperexcitability in the hippocampus.

The effects of zinc on neuronal excitability in rodent hippocampal slices were examined. In a paired-pulse protocol, the second population spike increased appreciably in the presence of zinc, whereas the first spike and the size of both population excitatory post-synaptic potentials remained unaffected. Changes in the second population spike produced by zinc were most pronounced when the afferents were stimulated with paired-pulses separated by 8-40 ms. The magnitude of altered excitability increased with the concentration of zinc in the perfusate. A long exposure to zinc in physiological concentration caused an epileptiform discharge followed by a period of depression. The effects of zinc could be mimicked with 1-3 microM bicuculline. We conclude that the integrity of the hippocampal inhibitory system is particularly vulnerable to zinc.

Long-lasting effects of partial hippocampal kindling on hippocampal physiology and function.

The objective of this project was to study the behavioral and physiological effects at 6-9 weeks after evoking 15 afterdischarges (ADs) in hippocampal CA1 (partial hippocampal kindling). Rats were trained on the open radial arm maze (RAM) with all eight arms baited, kindled, and then tested again on the RAM, followed by in vitro recordings at 8-9 weeks after kindling. Partial kindling was manifested by an increase in hippocampal AD duration. Enhancement of the commissural basal dendritic excitatory postsynaptic potential (EPSP) was observed for at least 1 day after the ADs. Kindled rats performed worse than control rats during the 1st but not during the 7th or 8th week after kindling. Rats that were slow in acquiring the RAM showed more RAM errors after kindling than those that showed fast acquisition. At 8-9 weeks after kindling, as shown by field potential recording in the hippocampal slice in vitro, kindled rats showed an increase in paired-pulse facilitation (PPF) of the EPSP in CA1 but a decreased PPF of the perforant path to dentate gyrus EPSP; no change in the PPF of the population spike was found in CA1 or DG. In a second group of rats that were not run on the RAM, at 6 weeks after kindling, PPF of the population EPSP and population spike were enhanced in the kindled rats compared to the control rats in CA1, but not in DG or CA3 in vitro (at 1.5, 2, or 4 times threshold intensity).(ABSTRACT TRUNCATED AT 250 WORDS)

Fast Multisite Optical Recording of Mono- and Polysynaptic Activity in the Hamster Suprachiasmatic Nucleus Evoked by Retinohypothalamic Tract Stimulation

Responses of the hamster suprachiasmatic nucleus (SCN) to retinohypothalamic tract (RHT) stimulation were studied in horizontal hypothalamic slices using fast multisite optical recording techniques. A 124-element photodiode detector array provided high-speed monitoring (0.5 ms/frame) of evoked neural activity in the SCN, while a larger 464-element photodiode array yielded improved spatial imaging with some loss in temporal resolution (1.6 ms/frame). Brief electrical stimulation of the optic nerves evoked a propagated compound action potential that was recorded optically as a single transient depolarization in many slice regions, including the SCN. Only within the SCN, however, was this optic tract signal followed by additional voltage-dependent optical responses which exhibited a fast and a slow depolarizing component. The initial upstroke of the fast component was Ca2+-insensitive and is presumed to reflect activity in presynaptic RHT afferents. The remainder of the fast depolarization and the slow depolarization were Ca2+-sensitive.These responses were labeled the early population excitatory postsynaptic potential (Early P.E.P.S.P.) and the Late P.E.P.S.P. respectively. The Late P.E.P.S.P. was not enhanced by K+ channel blockade, suggesting that glial depolarization is not the primary source of this component. Drugs known to suppress RHT-evoked SCN field potentials also suppressed the Early and Late P.E.P.S.P.'s recorded optically in the SCN. Unexpectedly, the Early P.E.P.S.P. was also reduced by the GABAA antagonist, bicuculline. Surface plots of normalized peak amplitudes showed that both SCN components had similar spatial distributions within the SCN, although the Early P.E.P.S.P. tended to be slightly more prominent within the medial SCN in some preparations. It is suggested that the Early P.E.P.S.P. represents firing of monosynaptically activated SCN neuron`s, while the Late P.E.P.S.P. reflects polysynaptic activity within the intrinsic SCN neuronal network that may be involved in the light entrainment of the circadian oscillator.

Development of inhibitory and excitatory synaptic transmission in the rat dentate gyrus

We studied the ontogeny of inhibitory and excitatory processes in the rat dentate gyrus by examining paired-pulse plasticity in the hippocampal slice preparation. The mature dentate gyrus produces characteristic paired-pulse responses across a wide range of interpulse intervals (IPI). Paired-pulse effects on population excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were analyzed at postnatal day 6 (PN6), PN7/8, PN9/10, PN15/16, and PN > 60. The synaptic paired-pulse profile (10-5,000 ms IPI) matured by PN7/8. The triphasic pattern of short-latency depression, a relative facilitation at intermediate intervals, and long-latency depression was present at all ages tested. Paired-pulse effects on granule cell discharge indicated the presence of weak short-latency (20 ms IPI) inhibition at PN6, the earliest day that a population spike could be evoked. By PN7/8, short-latency inhibition was statistically equivalent to the mature dentate gyrus. Long-latency (500-2,000 ms IPI) PS inhibition was present, and equal to the mature dentate gyrus by PN6. The most consistent difference between the mature and developing dentate gyrus occurred at intermediate IPIs (40-120 ms) where spike facilitation was significantly depressed in the development groups. The studies indicate that short-term plasticity matures rapidly in the dentate gyrus and suggest that the inhibitory circuitry can function at a surprisingly early age.

Augmenting action of nicotine on population spikes in the dentate gyrus of the guinea pig

Effects of nicotinic cholinergic agents on field potentials recorded from the dentate gyrus were studied in thin transverse sections of the hippocampus of the guinea pig. Nicotine augmented the population spike elicited by the second stimulus of a paired stimulation to the molecular layer. The threshold concentration of nicotine to cause this effect was 5–10 μM. The augmentation of the spike was not accompanied by an increase in the rising slope of population excitatory postsynaptic potentials, and was not observed in the presence of bicuculline. Carbamylcholine had a weak and inconsistent effect. D-tubocurarine and mecamylamine also augmented the population spike. The action of nicotine was blocked by hexamethonium. These results suggest that nicotine facilitates the generation of action potentials in granule cells by depressing inhibitory processes, and that properties of nicotinic cholinergic receptors are different in different subfields of the hippocampal formation, presumably reflecting the diversity of the receptors.