Commissural responses of rat retrohippocampal neurons

Synaptic responses of commissurally activated rat subicular and entorhinal neurons were studied intracellularly in vivo by stimulating the contralateral dentate gyrus. The most prominent synaptic responses in both subicular and entorhinal neurons were inhibitory postsynaptic potentials (IPSPs). IPSPs were generated in combination with antidromic spikes and/or excitatory postsynaptic potentials (EPSPs) and orthodromic spikes. No dependency between any two response types were found. Commissurally projecting subicular neurons (identified by the presence of antidromic spikes evoked by contralateral stimulation) were found, extending previous anatomical studies. Commissurally projecting entorhinal neurons were found in layer II, confirming previous anatomical studies. Positive correlations between antidromic spike latency and depth of recording sites supported the interpretation that axons projected along the fiber bundles of the hippocampal commissures and angular bundle to distribute to their targets. Possible circuits that could have mediated the excitatory and inhibitory responses of these retrohippocampal neurons are considered.     

The site for initiation of action potential discharge over the somatodendritic axis of rat hippocampal CA1 pyramidal neurons

Early electrophysiological studies in the mammalian hippocampus reported that orthodromic depolarization of pyramidal cells evoked action potential discharge (presumed Na+ dependent) both at the axon hillock and at one or more sites in the dendritic arborization (Cragg and Hamlyn, 1955; Andersen, 1959, 1960; Spencer and Kandel, 1961; Andersen and Lomo, 1966). Although tetrodotoxin (TTX)-sensitive spikes have been recorded at the dendritic level (Wong et al., 1979; Benardo et al., 1982; Miyakawa and Kato, 1986; Turner et al., 1989), the site for initiation of these potentials has not yet been determined. In this study, we examine the site for initiation of Na+ spike discharge over the cell axis of rat hippocampal CA1 pyramidal neurons. Intrasomatic and intradendritic recordings were obtained from pyramidal neurons of hippocampal slices maintained in vitro. Spike discharge was evoked by alvear (antidromic) stimulation or orthodromically by stimulation of afferent inputs in stratum oriens (SO) or stratum radiatum (SR). Antidromic and orthodromic spikes were greatest in amplitude in somatic recordings and declined over the apical dendritic axis, while spike half-width was shortest at the cell body and increased with distance from stratum pyramidale. Measurements of orthodromic spike threshold revealed that the only location at which spikes discharged at a consistent membrane potential at threshold intensity (voltage threshold) was the cell body region. Finally, at threshold intensity, SR-evoked intradendritic spikes were blocked by local application of TTX in stratum pyramidale, while spike blockade at suprathreshold intensity required the diffusion of TTX into the apical dendritic region. These results indicate that, for threshold intensities of stimulation, antidromic and orthodromic spike discharge in CA1 pyramidal cells is initiated in the region of the cell body layer, subsequently conducting over the apical dendrites in a retrograde fashion. In contrast, SR-evoked orthodromic spike discharge exhibits an intensity-dependent shift in the site of origin up to 200 microns within the apical dendritic arborization.     

Tolbutamide blocks postsynaptic but not presynaptic effects of adenosine on hippocampal CA1 neurones

Summary. Extracellular recording in the CA1 pyramidal cell layer of rat hippocampal slices was used to examine the effect of the ATP-sensitive potassium channel blocker tolbutamide and the channel opener levcromakalim on responses to adenosine. Tolbutamide 1 mM blocked the inhibitory effect of adenosine on the size of orthodromic population spikes but had no effect on the inhibitory action of adenosine on field EPSPs. Tolbutamide also blocked the suppression by adenosine of repetitive antidromic spikes induced in calcium-free media with high magnesium but did not prevent the effects of baclofen. Levcromakalim 100 μM potentiated inhibitory effect of adenosine, but not baclofen, on orthodromic population spikes. The results show that at postsynaptic, but not presynaptic, sites adenosine may activate an ATP-sensitive potassium channel. Accepted December 15, 1997; received September 9, 1997     

Inhibition of excitatory synaptic transmission by trans-resveratrol in rat hippocampus

The red wine polyphenol trans-resveratrol has been found to exert potent protective actions in a variety of cerebral ischemia models. The neuroprotection by trans-resveratrol thus far is mainly attributed to its intrinsic antioxidant properties. In the present study, the effects of the red wine polyphenol on excitatory synaptic transmission were investigated in the CA1 region of rat hippocampal slices. Perfusion with trans-resveratrol (10-100 microM) caused a concentration-dependent inhibition on the filed excitatory postsynaptic potentials (the field EPSPs) without detectable effect on the presynaptic volleys. The inhibition had a slow onset and was reversible. Trans-resveratrol (30 microM) did not change the ratios of paired-pulse facilitation of the field EPSPs tested at intervals of 20, 40 and 80 ms, nor did it alter the membrane properties of postsynaptic CA1 pyramidal neurons. However, trans-resveratrol (30 microM) significantly suppressed glutamate-induced currents in postsynaptic CA1 pyramidal neurons. In dissociated hippocampal neurons, the IC(50) value of trans-resveratrol in inhibition of glutamate-induced currents was 53.3+/-9.4 microM. Kainite and NMDA receptors were more sensitive to the red wine polyphenol than AMPA receptors. The present study for the first time demonstrates that trans-resveratrol inhibits the postsynaptic glutamate receptors, which probably works in concert with its antioxidant action for ameliorating the brain ischemic injury. The findings also support the future use of trans-resveratrol in the treatment of various neurodegenerative disorders.     

A purinergic component of the excitatory postsynaptic current mediated by P2X receptors in the CA1 neurons of the rat hippocampus

The pyramidal neurons in the CA1 area of hippocampal slices from 17- to 19-day-old rats have been investigated by means of patch clamp. Excitatory postsynaptic currents (EPSCs) were elicited by stimulating the Schaffer collateral at a frequency below 0.2 Hz. It was found that inhibition of glutamatergic transmission by 20 μm 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 100 μm 2-amino-5-phosphonovaleric acid (D-APV) left a small component of the EPSC uninhibited. The amplitude of this residual EPSC (rEPSC) comprised 25 ± 11% of the total EPSC when measured at a holding potential of ?50 mV. The rEPSC was blocked by selective P2 blocker pyridoxal phosphate-6-azophenyl-2′-4′-disulphonic acid (PPADS) 10 μm and bath incubation with non-hydrolysable ATP analogues, ATP-γ-S and α,β-methylene-ATP at 50 and 20 μm , respectively. The rEPSC was dramatically potentiated by external Zn²⁺ (10 μm ). In another series of experiments exogenous ATP was applied to the CA1 neurons in situ. An inward current evoked by ATP was inhibited by PPADS to the same extent as the rEPSC. It is concluded that, depending on membrane voltage, about one-fifth to one-quarter of the EPSC generated by the excitatory synaptic input to the hippocampal CA1 neurons of rat is due to the activity of P2X receptors.     

5-HT(1A) and 5-HT(7) receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission

We have studied the effects of 5-HT(1A) and 5-HT(7) serotonin receptor activation in hippocampal CA3-CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5-HT or 8-OH DPAT, a mixed 5-HT(1A)/5-HT(7) receptor agonist, inhibited AMPA receptor-mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5-HT(1A) receptor agonist 8-OH PIPAT and blocked by the 5-HT(1A) antagonist NAN-190. 8-OH DPAT increased paired-pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8-OH DPAT enhanced EPSC amplitude but did not alter paired-pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN-190 and was blocked by the 5-HT(7) receptor antagonist SB-269970. To confirm that EPSC enhancement was mediated by 5-HT(7) receptors, we used the compound LP-44, which is considered a selective 5-HT(7) agonist. However, LP-44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8-OH DPAT. These effects were respectively antagonized by NAN-190 and by SB-269970, indicating that under our experimental condition LP-44 behaved as a mixed agonist. 8-OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5-HT(1A) and 5-HT(7) receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5-HT(1A) receptors inhibit CA3-CA1 synaptic transmission acting both pre- and postsynaptically, whereas 5-HT(7) receptors enhance CA3-CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal-dependent cognitive functions. In this respect, we underline the need for new selective agonists of 5-HT(7) receptors.     

Asynchronic transmission in the CA3-CA1 hippocampal synapses in the neurological mutant taiep rat

For the taiep rat, a neurological mutant with severe astrogliosis secondary to demyelination, we have described alterations in spinal cord synaptic transmission. Asynchronous responses result from phasic action potential-derived glutamate release in this mutant. To evaluate whether this anomalous transmission is also produced in other regions of the taiep CNS and whether its nature involves a presynaptic or postsynaptic disruption, we studied the CA3-CA1 hippocampal synapses. Excitatory postsynaptic currents (EPSC) evoked by stimulation of Schaffer collaterals were recorded from CA1 pyramidal cells on picrotoxin-treated slices. Initial fast and time-locked EPSCs were evoked by conventional stimulation in both control and taiep neurons, showing similar latency and amplitude values unimodally distributed. In a high percentage of taiep neurons (47%), the initial EPSC was frequently followed by additional asynchronous synaptic currents (EPSC(ASYN)) with latencies ranging from 10 to 300 msec. As with initial EPSCs, EPSC(ASYN) were action potential dependent, sensitive to tetrodotoxin, and blocked by D-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. The occurrence probability of these events decayed monoexponentially as a function of poststimulus time. The elevation of extracellular Ca(2+) induced a reduction of amplitudes and a rate increase of EPSC(ASYN), in parallel with a reduction of paired pulse facilitation of initial EPSCs. The presynaptic fiber volley, extracellularly recorded, showed no significant differences between groups, with similar mean values of area and decay time. These findings in hippocampal circuitry suggest that, in taiep, the asynchronous evoked activity represents a rather generalized phenotype of the glutamatergic synapses and that EPSC(ASYN) seems to be determined by presynaptic alterations.     

Glutamate‐induced depression of EPSP–spike coupling in rat hippocampal CA1 neurons and modulation by adenosine receptors

The presence of high concentrations of glutamate in the extracellular fluid following brain trauma or ischaemia may contribute substantially to subsequent impairments of neuronal function. In this study, glutamate was applied to hippocampal slices for several minutes, producing over‐depolarization, which was reflected in an initial loss of evoked population potential size in the CA1 region. Orthodromic population spikes recovered only partially over the following 60 min, whereas antidromic spikes and excitatory postsynaptic potentials (EPSPs) showed greater recovery, implying a change in EPSP–spike coupling (E–S coupling), which was confirmed by intracellular recording from CA1 pyramidal cells. The recovery of EPSPs was enhanced further by dizocilpine, suggesting that the long‐lasting glutamate‐induced change in E–S coupling involves NMDA receptors. This was supported by experiments showing that when isolated NMDA‐receptor‐mediated EPSPs were studied in isolation, there was only partial recovery following glutamate, unlike the composite EPSPs. The recovery of orthodromic population spikes and NMDA‐receptor‐mediated EPSPs following glutamate was enhanced by the adenosine A1 receptor blocker DPCPX, the A_2A receptor antagonist SCH58261 or adenosine deaminase, associated with a loss of restoration to normal of the glutamate‐induced E–S depression. The results indicate that the long‐lasting depression of neuronal excitability following recovery from glutamate is associated with a depression of E–S coupling. This effect is partly dependent on activation of NMDA receptors, which modify adenosine release or the sensitivity of adenosine receptors. The results may have implications for the use of A₁ and A_2A receptor ligands as cognitive enhancers or neuroprotectants.     

Hippocampal mossy fibers induce assembly and clustering of PSD95-containing postsynaptic densities independent of glutamate receptor activation.

Factors that regulate the formation, spatial patterning, and maturation of CNS synapses are poorly understood. We used organotypic hippocampal slice cultures derived from developing (P5-P7) rat to test whether synaptic activity regulates the development and organization of postsynaptic structures at mossy fiber (MF) giant synapses. Antibodies to a prominent postsynaptic density (PSD) scaffold protein, PSD95, identified large (>1 microm) and irregularly shaped PSD assemblies that codistributed with synapsin-I or metabotropic glutamate receptor 7b (mGluR7b) -immunolabeled MF terminals in area CA3. To investigate the spatial organization of synaptic PSDs on individual pyramidal cells, neurons in slice cultures were transfected with a vector encoding a GFP-PSD95 fusion protein. Confocal three-dimensional reconstructions revealed clusters of PSDs along proximal dendrites of transfected pyramidal neurons in area CA3, but not in CA1. Clusters averaged 7.6 microm in length (range, 2.2-29 microm) and contained up to 35 individual PSDs (mean, 8.3). PSD clusters failed to form when slices were cultured without MFs, indicating that MFs induce cluster assembly. Chronic blockade of N-methyl-D-apartate- and AMPA/kainate-type glutamate receptors did not disrupt MF targeting or de novo formation of PSD clusters with a normal distribution on target cells. Additionally, glutamate receptor blockers did not alter the ultrastructural development of MF giant synapses containing multiple puncta adherens-like junctions and asymmetric synaptic junctions at dendritic shaft and spine domains, respectively. The results indicate that MF axons can induce the assembly and clustering of PSD95-containing postsynaptic complexes, displaying a normal subcellular and tissue distribution, by mechanisms that are independent of ionotropic glutamate receptor activation.     

Effects of a spider toxin (JSTX) on hippocampal CA1 neurons in vitro

The effect of a toxin (JSTX) obtained from Nephila clavata (Joro spider) on the CA1 pyramidal neurons of the hippocampus was studied using slice preparations. JSTX blocked the excitatory postsynaptic potentials (EPSPs) in the pyramidal neuron evoked by Schaffer collateral stimulation but was without effect on the antidromic action potentials or on the resting conductance. Depolarization induced by ionophoretic application of glutamate was readily suppressed by JSTX but aspartate-induced depolarization was much less sensitive to the toxin. Among preferential agonists activating 3 receptor subtypes for excitatory amino acids, quisqualate responses were most effectively suppressed by JSTX. Kainate responses were similarly suppressed but in some cells higher concentration of the toxin was needed to block the responses. N-methyl-D-aspartate (NMDA) responses were the least sensitive to JSTX but they were suppressed by +/- 2-amino-5-phosphonovaleric acid (APV). Long term potentiation (LTP) once it had taken place was not completely inhibited by APV. In the presence of JSTX, however, LTP was blocked and tetanic stimuli produced only a short-lived potentiation. In Mg2+ free solution, an orthodromic stimulation evoked repetitive spike responses which were superimposed on the depolarization following the initial spike. APV suppressed the depolarization and associated spikes leaving an orthodromic response which was sensitive to JSTX. The results suggest that JSTX blocks EPSPs in CA1 pyramidal neurons which are mediated by non-NMDA type receptors.     

Inhibitory function of zinc against excitation of hippocampal glutamatergic neurons

The function of zinc released from the neuron terminals is poorly understood. Here, the action of zinc in excitatory neurotransmission in rat hippocampal CA1 was studied by using in vivo microdialysis. Glutamate concentration in the perfusate was significantly decreased by perfusion with 10-300 microM ZnCl2, suggesting that presynaptic release of glutamate is inhibited by zinc in the CA1. While gamma-amino butyric acid (GABA) concentration in the perfusate was increased by perfusion with zinc. Furthermore, to study the action of zinc in postsynaptic response, the response of the CA1 pyramidal cells in the presence of 50 microM zinc was examined in the entorhinal cortex, which is connected with CA1 pyramidal cells. Perfusion of the hippocampal CA1 with zinc decreased glutamate concentration not only in the CA1, but also in the entorhinal cortex. The increase in glutamate concentration in the entorhinal cortex during perfusion of the CA1 with 50 microM glutamate was inhibited by the addition of zinc in the CA1. Zinc seems to be an inhibitory neuromodulator of glutamate release.     

Evidence for modulation of GABAergic neurotransmission by nicotine

Bath-application of nicotine (800 microM) to mouse hippocampal slices resulted in an increase in the amplitude of the population spike and the appearance of multiple population spikes in the CA1 pyramidal cell layer. Similar effects were observed after perfusion of the GABAA antagonist bicuculline methiodide (2 microM) and the glutamate decarboxylase inhibitor L-C-allylglycine (4 mM). These apparently excitatory effects of nicotine (800 microM) could be reversed by bath-application of gamma-aminobutyric acid (GABA; 400 microM), as well as by the GABA uptake inhibitor nipecotic acid (5 mM) and the benzodiazepine flurazepam (4 microM). Nicotine did not alter binding of [3H]GABA or [3H]flunitrazepam to whole brain plasma membranes. The results are consistent with the hypothesis that the electrophysiological effects of nicotine on CA1 pyramidal cell excitability is mediated by disruption of GABAergic transmission.     

Tetanic stimulation of schaffer collaterals induces rhythmic bursts via NMDA receptor activation in rat CA1 pyramidal neurons

Exploring the principles that regulate rhythmic membrane potential (Vm) oscillations and bursts in hippocampal CA1 pyramidal neurons is essential to understanding the theta rhythm (theta). Recordings were performed in vitro in hippocampal slices from young rats, and a group of the recorded CA1 pyramidal cells were dye-filled with carboxifluorescein and immunolabeled for the R1 subunit of the NMDA receptor. Tetanic stimulation of Schaffer collaterals (SCs) and iontophoresis of glutamate evoked rhythmic Vm oscillations and bursts (approximately 10 mV, approximately 7 Hz, 2-5 spikes per burst) in cells (31%) placed close to the midline ("medial cells"). Rhythmic bursts remained under picrotoxin (10 microM) and Vm oscillations persisted with tetrodotoxin (1.5 microM), but bursts were blocked by AP5 (25 microM) and Mg2+-free solutions. Depolarization and AMPA never induced rhythmic bursts. The rest of the neurons (69%), recorded closer to the CA3 region ("lateral cells"), discharged rhythmically single repetitive spikes under SC stimulation and glutamate in control conditions, but fired rhythmic bursts under similar stimulation, both when NMDA was applied and when non-NMDA receptors were blocked with CNQX (20 microM). Medial cells exhibited a larger NMDA current component and a higher NMDAR1 density at the apical dendritic shafts than lateral cells, suggesting that these differences underlie the dissimilar responses of both cell groups. We conclude that the "theta-like" rhythmic oscillations and bursts induced by glutamate and SC stimulation relied on the activation of NMDA receptors at the apical dendrites of medial cells. These results suggest a role of CA3 pyramidal neurons in the generation of CA1 theta via the activation of NMDA receptors of CA1 pyramidal neurons.     

Effect of trans-ACPD, a specific agonist of glutamate interacting with metabotropic receptors, on synaptic transmission in the rat hippocampus]

Trans-ACPD, a cyclic analogue of glutamate, has been studied for its influence on field potentials and excitatory postsynaptic currents (EPSCs) in the CA1 layer. Being applied in concentration 50 microM and above, trans-ACPD completely and reversibly inhibited excitatory postsynaptic field potentials but has no effect on EPSCs. Trans-ACPD in the same concentration reversibly reduced the amplitude of antidromic population spike in the CA1 layer, but has an insignificant effect on antidromic population spike in the CA3 layer.     

Nicotinic acetylcholine receptor-mediated synaptic potentials in rat neocortex

In the neocortex, fast excitatory synaptic transmission can typically be blocked by using excitatory amino acid (EAA) receptor antagonists. In recordings from layer II/III neocortical pyramidal neurons, we observed an evoked excitatory postsynaptic potential (EPSP) or current (EPSC) in the presence of EAA receptor antagonists (40-100 microM D-APV+20 microM CNQX, or 5 mM kynurenic acid) plus the GABA(A)-receptor antagonist bicuculline (BIC, 20 microM). This EAA-antagonist resistant EPSC was observed in about 70% of neurons tested. It had a duration of approximately 20 ms and an amplitude of 61.5+/-6.8 pA at -70 mV (n=35). The EAA-antagonist resistant EPSC current-voltage relation was linear and reversed near 0 mV (n=23). The nonselective nicotinic acetylcholine receptor (nAChR) antagonists dihydro-beta-erythroidine (DH beta E, 100 microM) or mecamylamine (50 microM) reduced EPSC amplitudes by 42 (n=20) and 33% (n=9), respectively. EPSC kinetics were not significantly changed by either antagonist. Bath application of 10 microM neostigmine, a potent acetylcholinesterase inhibitor, prolonged the EPSC decay time. EAA-antagonist resistant EPSCs were observed in the presence of antagonists of metabotropic glutamate, serotonergic (5-HT(3)) and purinergic (P2) receptors. The EAA-antagonist resistant EPSC appears to be due in part to activation of postsynaptic nAChRs. These results suggest the existence of functional synaptic nAChRs on pyramidal neurons in rat neocortex.     

Evoked CA3 field potentials corresponding to both EPSPs and IPSPs in hippocampal slice.

Biphasic field potentials were recorded in the CA3 distal dendritic region in response to both antidromic (fornix) and orthodromic (mossy fiber) stimulation in guinea pig hippocampal slices in vitro. The positive component (P1) corresponded to intracellularly recorded excitatory postsynaptic potentials. The negative component (N1) appears to be due to GABAA-mediated inhibitory postsynaptic potentials (IPSPs) since it corresponded to the fast IPSP recorded intracellularly, was blocked by bicuculline and penicillin and augmented by barbiturates. The amplitude of N1 and the duration of P1 are sensitive and useful measures of the GABAA-mediated IPSP.     

Δ-Tetrahydrocannabinol and the hippocampus: Effects on CA1 field potentials in rats

The effects of Δ⁹-tetiahydrocannabinol (THC) on ortho- and antidromically elicited CA1 field potentials were observed in locally anesthetized rats and in rats anesthetized with urethane. THC augmented amplitudes of population EPSP's as well as orthodromic and antidromic population spikes from pyramidal cells in locally anesthetized animals. Latencies to peak amplitude of these responses were increased. Conditioning-test shock experiments revealed that THC also depressed recurrent inhibition probably mediated by basket cells. In animals under urethane anesthesia THC enhanced test responses, but failed to augment population responses to the conditioning stimulus. It was concluded that THC enhanced postsynaptic excitatory processes but attenuated recurrent inhibition. Urethane anesthesia completely blocked the postsynaptic excitatory effect of THC but had little apparent influence on THC's disinhibitory action.     

A hypoxic injury potential in the hippocampal slice

In rat hippocampal slices, neurons in the stratum pyramidale of the CA1 were stimulated orthodromically and antidromically while the resultant extracellular population spikes were monitored. Hypoxic conditions were then induced. After disappearance of the orthodromic population spike, a second orthodromic population spike appeared. We have titled this the hypoxic injury potential since it reflects the onset of permanent injury to neurons in area CA1 of the hippocampus.     

A comparison of recurrent inhibition and of paired-pulse facilitation in hippocampal slices from normal and genetically epileptic mice.

Tottering mice exhibit inherited generalized epilepsy of the 'absence' type. In hippocampal slices from these mutant mice studied in vitro, pairing an alvear antidromic stimulus to an orthodromic one revealed a strong recurrent inhibition (RI) of CA1 pyramidal neurons. RI was maximal at 10 ms inter-pulse interval (IPI 70% decrease of population spike, PS) gradually decreasing to 15% at 320 ms IPI. At 10 ms IPI it shifted the input/output curves to the right and decreased maximum PS. In the group of slices from epileptic mice the early part of RI (2.5-60 ms) was indistinguishable from that of normal mice, with respect to both its strength and its liability to activity-dependent decrement induced by a train of antidromic stimuli (8 s, 5 Hz). However, the delayed part (80-320 ms) was slightly stronger in the epileptic group. Also in this group only the train of antidromic pulses caused a significant and lasting decrease in the unconditioned orthodromic PS. Paired-pulse facilitation was equally strong in the 2 groups of slices. It is concluded that mechanisms underlying epileptogenic hyperexcitability in the tottering mutant may not include a failure of inhibition, at least in the CA1 area of the hippocampus. On the contrary some inhibitory mechanisms may be stronger.     

Preconditioning by motor activity protects rat hippocampal CA1 neurons against prolonged ischemia

Recovery of orthodromic and antidromic population spikes in CA1 hippocampal slices of 30-day-old Wistar rats has been studied in the reperfusion period after prolonged (90 min) decapitation ischemia with and without preceding 15 min long non-voluntary motor activity of intact animals. The preconditioning motor activity significantly enhances the resistance of pyramidal neurons to ischemia at a temperature of 30 degrees C. The period of protection lasts for up to 40 min after the end of motor activity. In case the ischemia was started within 5-10 min after the preconditioning, complete restoration of the field potentials to preischemic control level could be achieved. These data are the first indication of the neuroprotective effect of preconditioning motor activity in CA1 damage after prolonged global ischemia.