Neurons In Field CA1 Research Articles

The role of dopamine-dependent negative feedback in the hippocampus-basal ganglia-thalamus-hippocampus loop in the extinction of responses

A mechanism for the extinction of the responses of hippocampal and dopaminergic neurons to repeated sensory stimuli is proposed, based on dopamine-dependent negative feedback in the hippocampus-basal ganglia-thalamus-hippocampus loop. Activation of hippocampal neurons evoked by a new stimulus facilitates the appearance of responses in dopaminergic neurons as a result of disinhibition via striopallidal cells of the nucleus accumbens and ventral pallidum. However, increases in dopamine levels and activation of D2 receptors on striopallidal cells, facilitating depression of hippocampal inputs, prevent disinhibition of dopaminergic neurons, such that their responses start to decline. Subsequent reductions in actions on D1 receptors lead to decreases in the efficiency of excitation both of neurons in hippocampal field CA1 and strionigral cells in the nucleus accumbens. The direct pathway via the basal ganglia mediates disinhibition of the thalamic nucleus reuniens, exciting neurons in field CA1, which leads to extinction of the responses of hippocampal neurons, decreases in disinhibition of dopaminergic cells, and further extinction of their responses.

Protective effects of interleukin-10 on the development of epileptiform activity evoked by transient episodes of hypoxia in rat hippocampal slices

The aim of the present work was to study the effects of interleukin-10 at concentrations of 1 and 10 ng/ml on the development of epileptiform discharges evoked in pyramidal neurons in field CA3 in rat hippocampal slices by transient episodes of hypoxia. Three 3-min episodes of hypoxia led to decreases in the generation threshold for evoked trains of population spikes and an increase in the number of population spikes per train in pyramidal neurons of field CA1. Interleukin-10 at a concentration of 1 ng/ml completely eliminated the development of epileptiform activity, while its protective effect was less marked at a concentration of 10 ng/ml. These effects of interleukin-10 on living hippocampal slices in in vitro conditions show that they may be associated with the functions of this cytokine as an intercellular mediator of the central nervous system itself rather than being mediated by the peripheral immune system. The results of these studies provide the first experimental evidence of the action of the anti-inflammatory cytokine interleukin-10 on the development of hypoxia-evoked epileptiform events in the hippocampus.

Limited plasticity of difference neurons in the visual cortex and hippocampus in rabbits during the oddball (random substitutions) test

The activity of 41 visual cortex neurons and 20 hippocampal field CA1 neurons was studied in rabbits during application of the oddball stimulation paradigm using color stimuli of different intensities. Among these cells, about one third were plastic cells (34% of cortical cells and 37% of hippocampal cells). These neurons showed significant increases in late responses, at times 200-500 and 200-1000 msec for visual cortex neurons and 300-550 msec for hippocampal neurons, to rare deviant stimuli of lesser intensity as compared with responses to the frequent standard stimuli of greater intensity. The initial peak of the response (40-120 msec), the "difference discharge," remained stable in responses to deviant and standard stimuli throughout the experiment. It is suggested that the strengthening of the late components of neuron responses to rare deviant stimuli (limited plasticity) reflects inclusion of the mechanisms of the orientational reflex.

Hyperexcitability of pyramidal neurons in field CA1 in hippocampal slices from rats evoked by episodes of hypoxia: The roles of GABAA and GABAB receptors

Hyperexcitability of pyramidal neurons in field CA1 in hippocampal slices from rats evoked by episodes of hypoxia: The roles of GABAA and GABAB receptors

Hyperexcitability of Neurons in Field Ca1 Evoked by Transient Episodes of Hypoxia in Hippocampal Slices from Rats of Different Ages

Hyperexcitability of Neurons in Field Ca1 Evoked by Transient Episodes of Hypoxia in Hippocampal Slices from Rats of Different Ages

Studies of the mechanism of development of "deprivation" potentiation of population responses of neurons in field CA1 of living hippocampal slices.

Experiments on rat hippocampal slices were performed with testing of the synaptic connections of Schaffer collaterals and neurons in field CA1 to study the effects of interrupting low-frequency test stimulation (0.05 Hz) on the amplitude of population spikes. These studies demonstrated a correlation between the duration of pauses in stimulation (form 10 to 120 min) and increases in the amplitude of spikes (on average by 30-100% of baseline response magnitude). This "deprivation" potentiation was additive and could persist for long periods of time (testing was up to 1 h). Preliminary induction of long-term post-tetanic potentiation, which prevented the subsequent development of the late, but not the shortterm phase, for 1-3 h, led to suppression of the development of "deprivation" potentiation after a 60-min pause in stimulation. Similar results were obtained in experiments using 20 microM polymyxin B, which blocks protein kinase C and the PKC-dependent phase of long-term post-tetanic potentiation; this is evidence supporting the previously advanced hypothesis that the development of deprivation potentiation and the late. PKC-dependent phase of long-term post-tetanic potentiation share common mechanisms, associated with people phosphorylation.

Chapter 11 Modification of dendritic development

Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the hippocampal Ammon's horn and, particularly, on the CA1 field pyramidal neurons, as well as on afferences to the hippocampus which needs to be further investigated.

Intrasynaptic ephaptic feedback in central synapses.

Electrophysiological laboratory studies on rat visual cortex and hippocampus slices are reviewed. The aim was to confirm the existence of positive feedback in central synapses operating by an electrical (ephaptic) mechanism, as suggested by Byzov. Byzov's hypothesis holds that artificial hyperpolarization of the postsynaptic membrane potential should increase the amplitude of the excitatory postsynaptic current (EPSC) and potential (EPSP) in some central synapses not only by means of increases in the electromotive force (EMF). but also by means of increases in transmitter release from the presynaptic apparatus. Some experiments showed that hyperpolarization altered the parameters of presynaptic transmitter release, i.e., the quantity of "failed" responses N0, the coefficient of variation CV, and the quantum composition m of minimal EPSC and EPSP. The effect was particularly marked for EPSP in giant synapses formed by mossy fibers on neurons in field CA3. "Supralinear" functions were observed for these synapses in the relationship between EPSC amplitude and membrane potential in conditions of hyperpolarization of membrane potentials and in the relationship between presynaptic paired-stimulus facilitation and membrane potential. All of these "non-classical" effects disappeared when summed rather than minimal EPSC were evoked. The results are in agreement with computer experiments based on the Byzov model and are regarded as support for Byzov's hypothesis. Regardless of their explanation, the data obtained here demonstrate a new feedback mechanism for central synapses, which allows the postsynaptic neuron to control the efficiency of some synapses via changes in membrane potential. This mechanism can significantly increase the efficiency of large ("perforated") synapses and explains the increase in the number of this type of synapse after various experimental manipulations, such as those inducing long-term potentiation or forming conditioned reflexes.

Intracellular studies of the interaction between paired-pulse facilitation and the delayed phase of long-term potentiation in the hippocampus.

The mechanisms of the early (up to 1 h) and late (up to 3 h) phases of long-term potentiation were studied by analyzing the interaction between long-term potentiation and presynaptic paired-pulse facilitation. "Minimal" excitatory postsynaptic potentials were measured in pyramidal neurons in field CA1 of rat hippocampal slices in conditions of paired-pulse stimulation of the radial layer. In most neurons, paired-pulse facilitation decreased after induction of long-term potentiation, and this reduction lasted throughout the recording period (up to 3.5 h). Changes in paired-pulse facilitation correlated with the extent of long-term facilitation and with the initial level of paired-pulse facilitation, and the extent of facilitation depended on the initial level of paired-pulse facilitation. This latter relationship was different for the early and late phases of long-term potentiation and increased with time. Overall, the data obtained here demonstrate a significant role for presynaptic mechanisms in maintaining both the early and late phases of long-term potentiation. It is suggested that the basic mechanism of the early phase of potentiation is an increase in the probability that transmitter will be released, which also leads to an increase in the number of effective release sites, due to transformation of "presynaptically quiet" synapses into effective synapses. It is proposed that the development of the late phase is based on simultaneous pre- and postsynaptic structural transformations which increase the number of synaptically active zones.

Loss of perikaryal parvalbumin immunoreactivity from surviving GABAergic neurons in the CA1 field of epileptic gerbils.

The Mongolian gerbil (Meriones unguiculatus) is known as a genetic model of epilepsy. Seizure behavior ranges from subtle events like arrest of motor activity and facial spasms to grand mal seizures followed by automatisms. Exploratory behavior in a stressful situation represents the most effective environment for provoking seizures in gerbils. Modifications of the inhibitory hippocampal circuits have been suggested as a cause of seizure susceptibility in the gerbil. This study presents a quantitative analysis of the hippocampal parvalbumin (PV)-immunoreactive and gamma-aminobutyric acid (GABA)-immunoreactive neurons in gerbils whose seizure sensitivity had been scored. PV is a cytosolic calcium-binding protein synthesized by a subpopulation of GABAergic neurons and thought to be responsible for the fast spiking capability of this subset of neurons. We show that the number of PV-immunoreactive neurons in the CA1 field of the gerbil hippocampus decreases in repeatedly seizing animals as compared to non-seizing controls. The lowest density of PV-immunoreactive neurons was observed 1 hour after the last generalized seizure. No changes in the density of GABA-immunoreactive neurons in field CA1 paralleled the obvious loss of perikaryal PV-immunoreactivity. The CA1 field represents the final output region to extrahippocampal brain areas, and its recruitment or not into seizure activity is crucial for the spreading of hippocampal discharges to the adjacent neocortex. A reduction of such a calcium-buffering system in the soma and dendrites may affect the spike characteristics of PV-containing GABAergic neurons and may alter their response to glutamatergic transmission. A reduced inhibitory control of pyramidal cells may ensue, facilitating neuronal excitability as a result.

Origins of the variations in long‐term potentiation between synapses in the basal versus apical dendrites of hippocampal neurons

Responses to theta pattern stimulation, and the long-term potentiation (LTP) they induce, were compared in the basal versus apical dendrites of neurons in field CA1 of hippocampus. A series of 10 theta bursts produced more than twice as much LTP in basal synapses as in their apical counterparts as measured with field EPSPs. This confirms earlier field potential studies showing that the maximum degree of potentiation (the LTP ceiling) is considerably greater in stratum oriens than stratum radiatum. Experiments with whole-cell clamp recording obtained similar results, indicating that synapses at different loci on the same neuron reach different LTP ceilings following prolonged theta burst stimulation. The basal synapses also required fewer theta bursts to reach their LTP ceiling than did the apical synapses. Tests with paired-pulse facilitation and an antagonist of the NMDA receptor gave no indication that the greater LTP in basal synapses was qualitatively different from the lesser effect obtained in apical contacts. Intracellular recording revealed significant differences between basal versus apical responses to single theta bursts and trains of bursts: the within-burst depolarization was greater and the between-burst hyperpolarization was smaller for the basal dendritic responses. These two variables have previously been proposed to influence the magnitude of LTP and the observed differences between basal versus apical synapses are in accord with this hypothesis. Together with recently described immunocytochemical results, the findings reported here suggest that variations in LTP across dendritic subfields of hippocampus reflect a differential distribution of a subclass of GABAergic interneurons.

Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil: Brain microdialysis study

Ischemia-induced selective neuronal injury to field CA1 is not attributable to selective glutamate release in field CA1 during ischemia. Excessive release of glutamate has been proposed to play a major role in ischemia-induced selective neuronal death in field CA1 of the hippocampus. It is well known that, following carotid arterial occlusion of 5 min duration in the gerbil, the pyramidal neurons in field CA1 show delayed neuronal death, whereas the neurons in field CA3 do not show any neuronal degeneration. In the present study, we measured the levels of released glutamate during ischemia in field CA1 and field CA3, separately, and evaluated whether there are subregional differences in the concentration of released glutamate which could be a satisfactory explanation for the selective vulnerability of hippocampal neurons to ischemia. Extracellular glutamate levels were significantly increased during ischemia in both field CA1 and field CA3. No significant differences were detected in the time-course of change in glutamate release and the levels of glutamate between field CA1 and field CA3. This result indicates that the increased glutamate levels do not play a pivotal part in the detrimental effect of glutamate during 5-min ischemia. Some differentiated post-synaptic organization may act as a crucial factor in the development of ischemia-induced selective neuronal death in the gerbil hippocampus.

Autoradiographic analysis of [ 3H]ryanodine binding sites in rat brain: Regional distribution and the effects of lesions on sites in the hippocampus

Quantitative and qualitative autoradiographic methods together with lesion approaches were used to determine the distribution of [ 3H]ryanodine binding sites in rat brain and the neuronal localization of these sites in the hippocampus. In normal animals, levels of [ 3H]ryanodine binding sites ranged from a low of about 1 fmol/mg tissue in subcortical structures to a high of 12–18 fmol/mg tissue in subregions of the hippocampus and the olfactory bulb. Relatively high densities of sites (5–9 fmol/mg tissue) were also seen in the olfactory tubercle, most areas of the cerebral cortex, accumbens nucleus, striatum, lateral septal nuclei, pontine nucleus, superior colliculus and granule cell layer of the cerebellum. Specific binding was undetectable in white matter. In experimental animals, intracerebral injections of kainic acid caused neuronal degeneration and a near total depletion of [ 3H]ryanodine binding sites in the dentate gyrus and in fields CA1, CA2 and CA3 of the hippocampus. Injections of kainic acid that left dentate granule cells largely intact while destroying all neurons in field CA3 had no effect on binding sites in the dentate gyrus. However, these lesions substantially reduced the density of binding in field CA3, leaving a narrow band of sites outlining the position of the degenerated CA3 pyramidal cells. Mechanical knife-cut lesions that severed the granule cell mossy fiber input to field CA3 reduced the density of binding sites in the CA3 region. The results indicate that [ 3H]ryanodine binding sites in brain are heterogeneously distributed and suggest that a proportion of these sites in the hippocampus may be contained in mossy fiber terminals where a presumptive calcium channel/ryanodine receptor complex may be involved in the regulation of calcium mobilization and/or neurotransmitter release.