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J Lerma

Publications and source records attributed to J Lerma.

At least 55 records · Page 3Linked to original sources
PubMed1988

Sensory modulation of hippocampal transmission. I. Opposite effects on CA1 and dentate gyrus synapsis.

Neuronal transmission through hippocampal subfields exhibits a high degree of modulation and appears dependent on the behavioral state and hippocampal EEG. Sensory inputs, which profoundly modify the hippocampal EEG, may be involved in modulating hippocampal excitability. Field responses of the CA1 region, evoked by ipsilateral CA3 or perforant path stimulation, as well as dentate gyrus potentials evoked by perforant path stimulation were recorded in paralyzed and locally anesthetized rats and studied before, during and after sensory stimulation, consisting of gentle stroking of the animal's fur. On some occasions the CA1 was also antidromically driven from the posterior alveus in order to study the recurrent inhibitory loop and paired pulses were applied to the perforant pathway to study recurrent inhibition in the dentate gyrus. Evoked responses were averaged and field excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude measured. In addition the positive wave which follows the population spike, which corresponds in part to the recurrent IPSP, was also evaluated. Sensory stimulation, which evoked a high-amplitude 5-6 Hz theta (theta)-rhythm in the hippocampal EEG, drastically depressed the efficacy of Schaffer collateral volleys in discharging the CA1 cells. The EPSP-PS curves, however, were not altered revealing that cellular excitability was unaffected. The inhibitory CA1 loop appeared to be unaltered. In contrast, the dentate gyrus responses to perforant pathway stimulation were enhanced during periods of sensory stimulation and the cellular excitability increased, as judged by the shift to the left of EPSP-PS relation. In addition, the recurrent inhibition appeared to be reduced during sensory stimulation. Present results demonstrate that sensory stimulation causes modulation of information transfer through the hippocampus. This modification of hippocampal transmission may serve to properly gate the information reaching the CA1 and dentate gyrus.

Action Potentials↗
PubMed1988

Sensory modulation of hippocampal transmission. II. Evidence for a cholinergic locus of inhibition in the Schaffer-CA1 synapse.

The present work studied the neurotransmitter mediating the depressive effect of sensory stimulation on the Schaffer-CA1 transmission. Field responses of the CA1 region evoked by ipsilateral CA3 stimuli were recorded in paralyzed, locally anesthetized rats following the same experimental paradigm as in the previous work. The tissue zone under recording was perfused in vivo by an implanted hollow fiber (brain dialysis device) with either Krebs-Ringer bicarbonate (KRB), or KRB with penicillin, atropine, acetylcholine or eserine. Results were the following: (1) atropine increased the field excitatory postsynaptic potential (EPSP) amplitude in a dose-dependent manner and totally abolished the modulatory action of sensory stimulation; (2) both the field EPSP and the modulatory action of sensory stimulation remained unaltered during the blockade of GABAergic activity by penicillin; (3) acetylcholine as well as eserine induced a great diminution of both field EPSP and population spike amplitudes, without altering the effect of sensory stimulation; (4) penicillin and atropine induced multiple population spikes, reversing the effect of sensory stimulation and increasing the cell excitability. These results demonstrate that the sensory modulation of information transfer through the Schaffer-CA1 synapse is mediated by a muscarinic cholinergic mechanism. The dose-dependent increase in the field EPSP by muscarinic blockade is evidence for the existence of a cholinergic presynaptic inhibition on the Schaffer collateral terminals.

Acetylcholine↗
PubMed1988

Does taurine act as an osmoregulatory substance in the rat brain?

The effects of hypotonic media on extracellular free amino acid levels were studied 'in vivo' in the rat dentate gyrus by means of the brain dialysis technique. Extracellular taurine levels increased specifically during perfusions with Krebs-Ringer bicarbonate in which the NaCl concentration was reduced by 25 or 50 mmol/l (hypotonic solutions). These taurine increases were markedly reduced in the presence of furosemide. With further NaCl reductions the enhanced taurine levels remained stable, whereas other amino acids such as glutamate started in increase in a dose-dependent manner. Isoosmolar replacement of NaCl by sucrose did not affect extracellular amino acid levels. These results indicate the possible involvement of taurine in osmoregulatory processes in the brain.

Amino Acids↗
PubMed1988

Low chloride-dependent release of taurine by a furosemide-sensitive process in the in vivo rat hippocampus.

Extracellular amino acid levels and field potentials evoked by perforant pathway stimuli were studied in vivo by means of a dialysis device, perfusing the rat dentate gyrus with low chloride solutions. When balanced with acetate, these perfusions enhanced the granule cell population spike amplitude. A specific extracellular taurine enhancement occurred whenever Cl- was replaced by acetate solution, reaching an increase of 20-fold over the basal taurine levels when 125 mM Cl- was replaced, whereas other amino acids remained unchanged. A considerable degree of Cl- replacement with iodide was needed, however, to obtain significant increases of extracellular taurine. Perfusions with bromide instead of Cl- did not cause any change in levels of extracellular amino acids including taurine. Furosemide, an inhibitor of Cl- transport, greatly reduced the taurine increase evoked by the low extracellular concentration of permeant anions. This drug also inhibited the taurine release induced by perfusion with 9 mM K+. These findings indicate that the extracellular increase of taurine, evoked by low permeant anion concentrations, may result from the taurine release through a furosemide-sensitive process.

Amino Acids↗
PubMed1988

Coexpression of N-methyl-D-aspartate and phencyclidine receptors in Xenopus oocytes injected with rat brain mRNA.

Recent evidence suggest that the N-methyl-D-aspartate (N-Me-D-Asp) channel is functionally and structurally associated with the phencyclidine (PCP) receptor, which mediates the psychotomimetic effects of PCP, sigma opioids, and dioxalanes. To investigate the relationship between N-Me-D-Asp and PCP receptors on a molecular level, we injected mRNA isolated from adult rat brain into Xenopus oocytes. In injected oocytes N-Me-D-Asp application (with glycine) evoked a partially desentizing inward current that was potentiated by glycine and blocked by D-(-)-amino-5-phosphonovaleric acid (D-APV), by Zn2+ and, in a voltage-dependent manner, by Mg2+. These results show that the distinguishing features of rat brain N-Me-D-Asp channels are reproduced in this translation system. In addition, kainic acid elicited a nondesensitizing inward current at short latency, and quisqualate elicited a delayed oscillatory inward current, presumably mediated by a second-messenger system. Responses to glutamate had both short-latency and delayed components. The PCP derivative N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) blocked the N-Me-D-Asp-evoked current, and its potency was comparable to its binding affinity in rat brain membranes. Onset of block required the presence of antagonist. Antagonism was stereoselective in that the active ligand dexoxadrol was a more effective blocker than its relatively inactive stereoisomer levoxadrol. adrol. Other PCP receptor ligands, (+)SKF-10,047 and MK-801, also blocked. Potencies of compounds active at N-Me-D-Asp and PCP receptors in oocytes were comparable to those obtained previously in electrophysiological and binding assays on neural tissues. These results indicate the coexpression of neuronal PCP and N-Me-D-Asp receptors in Xenopus oocytes.

Animals↗
PubMed1987

Characteristics of CA1 activation through the hippocampal trisynaptic pathway in the unanaesthetized rat.

The hippocampal CA1 field is activated by the entorhinal cortex mainly through the hippocampal excitatory trisynaptic circuit. Field responses of the CA1 region were evoked by ipsilateral CA3 or perforant path volley (mono- or trisynaptic activation, respectively) in paralyzed, locally anaesthetized rats and studied as a function of the stimulus patterns presented. The relationship of these responses with the concomitant EEG was also explored. Results showed that mono- and especially trisynaptically evoked responses were progressively enhanced by increasing the stimulus frequency from 0.1 to 1.0 Hz. At specific intensities the trisynaptically evoked population spike (PS) was present only with a rather fixed frequency of stimulation (approximately 0.5 Hz). PS was produced in 100% of the responses using 0.7 Hz, indicating the existence of a threshold-like level for this stimulus parameter. The frequency of presented paired pulses differentially affected pair-pulse facilitation of mono- and trisynaptically evoked excitatory postsynaptic potentials (EPSP): higher frequency decreased the former and increased the latter. All evoked responses studied (i.e. EPSP and PS) showed steep increments and decrements in amplitude, clearly developing several clusters. Moreover, the amplitude distribution of trisynaptic PS often varied spontaneously from maximal to negligible values, showing an all-or-none distribution. Clustering was interpreted as evidence of the existence in the hippocampus of functional neuronal aggregates. All-or-none distribution of trisynaptic PS was found to be associated with the EEG pattern, PS amplitude being maximal during irregular EEG activity and minimal during theta rhythm. Present results suggest that (1) the entorhinal cortex may exert modulatory actions on CA1 by a mechanism widely based on the frequency of the input; (2) information transfer from the entorhinal cortex to other brain areas throughout the hippocampus is biased by hippocampal EEG; and (3) electronic coupling may be functionally predominant in the hippocampus.

Animals↗
PubMed1987

Effects of dihydrokainic acid on extracellular amino acids and neuronal excitability in the in vivo rat hippocampus.

The effect of inhibition of the high-affinity uptake of glutamate on the extracellular concentration of amino acids and on neuronal excitability was studied in vivo in the hippocampus of the rat. The dentate gyrus or CA1 field were perfused through a dialytrode with Krebs-Ringer-bicarbonate or dihydrokainic acid solutions. The spontaneous electrical activity and evoked field potentials were recorded concomitantly at dendritic or somatic levels. The results showed that with dihydrokainic acid: the extracellular concentrations of both glutamate and taurine were markedly increased in both areas of the hippocampus, the response of taurine being greater in CA1, while other amino acids were unaffected; in the dentate gyrus, the field excitatory postsynaptic potential was decreased while the population spikes were augmented, indicating an increased excitability of the neuronal population. In CA1, both the excitatory postsynaptic potential and spikes were reduced in amplitude. These results indicate that changes in the extracellular concentration of endogenous glutamate influences excitability of the tissue and that inhibition of the uptake processes for putative amino acid neurotransmitters increases the postsynaptic action of synaptically-released endogenous amino acids.

Action Potentials↗
PubMed1986

In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis.

Extracellular (EC) concentrations of amino acids were determined in the rat dentate gyrus by means of non-linear regression analysis of 'in vivo' brain dialysis data, considering a simple model of diffusion through a dialysis membrane. The apparent diffusion constants (K) of several amino acids were also calculated in the 'in vivo' situation. While putative amino acid neurotransmitters (glutamate, aspartate and gamma-aminobutyric acid (GABA) were present in the EC fluid at the low micromolar range (0.8-2.9 microM), glutamine was by far the most prominent (193.4 microM). The values of intra/extracellular concentration ratios formed 3 groups: high (greater than 2000) for putative neurotransmitters; low (less than 100) for serine, glutamine, arginine and alpha-alanine; and intermediate (about 400) for taurine. The 'in vivo' calculated K values proved useful for estimation of both basal and changing EC concentrations of amino acids in relatively brief perfusions. These data were evaluated in terms of the functional significance of absolute EC concentrations and tissue-EC fluid ratios. Present findings indicate the simultaneous existence of both an inhibitory and an excitatory tonus as well as the utility of high intra/extracellular concentration ratios in determination of the possible neurotransmitter role of specific amino acids.

Amino Acids↗
PubMed1986

Variation of potassium ion concentrations in the rat hippocampus specifically affects extracellular taurine levels.

The effects of different K+ concentrations (3-100 mM) on both the extracellular amino acid levels and field potentials, evoked by perforant pathway stimulation, were studied 'in vivo' in the rat dentate gyrus by means of a brain dialysis device, formed by a hollow fiber plus a stainless-steel electrode. Perfusion with low K+ concentrations (3-12 mM; Krebs-Ringer bicarbonate) specifically enhanced the dialysate levels of taurine and concomitantly increased the population spike amplitude. High K+ concentrations in perfusate (greater than 25 mM) did not further increase the levels of taurine but enhanced both glutamate and gamma-aminobutyric acid levels, whereas the population spike diminished drastically. The absence of calcium ions in the perfusion liquid increased both basal and K+-enhanced taurine levels. The specific enhancement of extracellular taurine by physiological K+ concentrations may represent an autoregulative mechanism of nervous tissue excitability.

Action Potentials↗
PubMed1986

Abolition of CA1 population spike by sensory stimulation.

The effect of sensory stimulation, such as stroking of the animals' fur, on activation of the hippocampal CA1 field was studied in paralyzed and locally anaesthetized rats. CA1 population responses evoked either monosynaptically (ipsilateral CA3 stimulation) or trisynaptically (perforant pathway stimulation) decreased markedly when sensory stimulation was applied, and CA1 population spikes were absent during most periods of sensory stimulation. These results demonstrate the strong modulatory role of sensory inputs on hippocampal circuits.

Animals↗
PubMed1985

Electrophysiological evidence that nipecotic acid can be used in vivo as a false transmitter.

Dentate gyrus of the rat hippocampal formation was perfused with the potent inhibitor of GABA uptake, nipecotic acid, by means of an implanted dialytrode. Evoked population spikes in dentate gyrus were decreased in amplitude and often abolished during perfusion. However, multiple (2-4) population spikes developed shortly after nipecotic acid withdrawal. This excitability increase, which presented a pattern of repetitive discharge resembling that following blocking of GABAergic transmission was interpreted as electrophysiological evidence that nipecotic acid can act as a false transmitter 'in vivo', as previously postulated from uptake and release 'in vitro' studies.

Animals↗
PubMed1985

Hippocampal theta rhythm during paradoxical sleep. Effects of afferent stimuli and phase relationships with phasic events.

Hippocampal theta rhythm and phasic events (i.e., vibrissa, body and ocular movements and ponto-geniculo-occipital (PGO) spikes) were recorded in rats and cats during paradoxical sleep (PS). Single pulse stimulation of some afferent structures (i.e., medial septum, mesencephalic reticular formation and entorhinal cortex) were performed during PS. Hippocampal afferent stimulation determined the phase resetting of hippocampal theta waves during PS in a similar form to that during wakefulness. All studied phasic events tend to occur at a preferred phase of the theta cycle. Theta waves begin to synchronize some time before movements. These results suggest that PS is an active state during which hippocampal theta rhythm may have functions similar to those occurring during wakefulness, e.g. sensorimotor integration.

Afferent Pathways↗
PubMed1985

Aminobutyric acid greatly increases the in vivo extracellular taurine in the rat hippocampus.

The effects of gamma-aminobutyric acid (GABA) on the extracellular levels of taurine and on excitability in the dentate gyrus were studied in anesthetized rats by the dialytrode technique. The dentate gyrus was perfused by means of a dialytrode with Krebs-Ringer-bicarbonate or GABA solutions. Amino acid contents in perfusates and dentate field potentials evoked by electrical stimulation of the perforant pathway were evaluated. GABA drastically elevated the levels of extracellular taurine in a dose-dependent manner, decreasing the amplitude of the population spike. This result indicates that GABA stimulates taurine release, probably by a counter-transport process. It is suggested that in physiological conditions an increase in extracellular taurine may be produced by synaptically released GABA.

Animals↗
PubMed1984

Interactions between hippocampal penicillin spikes and theta rhythm.

The relationships between theta rhythm and epileptic spikes, evoked by penicillin, were studied in the rat hippocampus. Records were taped and processed off-line, and autocorrelation functions, averages and power spectra of the EEG and frequency histograms of the epileptic spikes were calculated. Results showed that: (1) epileptic spikes tend to occur in a preferred phase of theta rhythm; (2) they provoked a reset of the phase of theta rhythm, acting as internal stimuli; (3) epileptic spikes decreased in frequency and were often abolished when theta rhythm was evoked; (4) these effects appeared to be dependent on the medial septal pathway. These findings indicate the existence of an antagonism between two hippocampal phenomena (epilepsy and theta rhythm). On the other hand, they also seem to be interrelated since the generation of one is accompanied by a reciprocal decrease in the other.

Animals↗
PubMed1984

In vivo effects of nipecotic acid on levels of extracellular GABA and taurine, and hippocampal excitability.

The effect of nipecotic acid on the extracellular levels of the putative hippocampal inhibitory transmitters, gamma-aminobutyric acid (GABA) and taurine, and also excitability in the dentate gyrus, were studied in anaesthetised rats using the dialytrode technique. The dentate gyrus was perfused by means of a dialytrode , using Krebs-Ringer bicarbonate or nipecotic acid solutions. Dentate field potentials, evoked by electrical stimulation of the perforant pathway, were recorded. Nipecotic acid drastically elevated the levels of extracellular GABA and taurine and the amplitude of population spikes in the dentate was concomitantly decreased. These results indicate that changes in extracellular levels of endogenous GABA and/or taurine influence the excitability of the hippocampus.

Animals↗
PubMed1984

Dialytrode technology and local profiles of amino acids in the awake cat brain.

Methods to investigate the in vivo effects and release of neuroactive substances include cortical cups, push-pull cannulae, chemitrodes, and dialytrodes. Critical evaluation of these procedures is necessary in order to interpret related results and to select the most suitable devices for further studies. Recent improvements in the dialytrode include structural modifications and the use of a small, permeable membrane constructed of thin polyester. The dialytrode system and its diffusion rates have been characterized with in vitro studies. In vivo long-term experiments in awake cats have been conducted to test injection rates, diffusion of [14C]urea, temporal variability, pressure factors, and other experimental variables. Using dialytrodes we have measured the normal profile of amino acids present in different cerebral structures and their possible correlations.

Amino Acids↗