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G Richter-Levin

Publications and source records attributed to G Richter-Levin.

47 records · Page 3Linked to original sources
PubMed1990

Grafting of midbrain neurons into the hippocampus restores serotonergic modulation of hippocampal activity in the rat.

The ability of midbrain raphe (MR) cells grafted into serotonin-depleted brain to restore hippocampal responses to synaptically released serotonin was studied using a serotonin-releasing drug, D-fenfluramine (FFA). In normal rats, FFA enhances reactivity of the dentate gyrus (DG) to perforant-path stimulation, while suppressing spontaneous activity. These effects of the drug were dependent on the presence of normal serotonin neurotransmission in the hippocampus. Depletion of brain serotonin markedly attenuated DG reactivity to FFA. MR grafts (4-5 months after transplantation) restored the reactivity of the hippocampus to FFA. Immature MR grafts (3 weeks after transplantation) or septal control grafts could not reproduce the effects of mature grafts. These experiments demonstrate the possible functional incorporation of neural transplants in a host brain and the possible involvement of these grafts in regulation of normal host electrical activity. The combined utilization of a serotonergic graft and a releasing drug (i.e. FFA), in the serotonin-deprived brain, allows the study of serotonin functions in restricted parts of the brain.

Action Potentials↗
PubMed1990

Effects of serotonin releasers on dentate granule cell excitability in the rat.

Serotonin modulating effects on hippocampal electrical activity were studied using serotonin releasing drugs (e.g. d-fenfluramine, FFA, and p-chloroamphetamine, PCA). FFA and PCA enhanced the reactivity of the dentate gyrus to stimulation of the perforant path (PP) in the anesthetized rat. The population spike (PS) but not the population EPSP (EPSP) was enhanced by FFA indicating that the drug effect is not exerted at the PP synapse, but at some postsynaptic site between the synapse and the spike generation mechanism. A depth profile of the response to PP stimulation indicated that the largest effect of FFA was present just below the granular cell layer. There were no systematic effects of FFA on the EPSP at any depth tested. The effect of FFA was much reduced in rats depleted of serotonin by p-chlorophenylalanine (PCPA) and restored when serotonin stores were repleted by the serotonin precursor 5-hydroxytryptophane (5-HTP). d-FFA was at least twice as effective as 1-FFA in enhancing responses in the dentate gyrus (DG). In noradrenaline (NA) depleted rats the increase in PS size was as in control rats. The effects of FFA were blocked by the 5-HT1a antagonist spiperone but not by the 5-HT2 antagonist mianserin. These results suggest that the effect of FFA is primarily due to release of serotonin from its terminals. At the gross electrographic level, FFA suppressed spontaneous sharp wave activity and reduced the magnitude of hippocampal EEG. Spontaneous extracellular single unit activity, recorded in the DG, was also inhibited by FFA concomitantly with the increase in the PS size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Raphe cells grafted into the hippocampus can ameliorate spatial memory deficits in rats with combined serotonergic/cholinergic deficiencies.

The ability of embryonic raphe cells grafted into the hippocampus to restore spatial learning ability was tested in rats with combined serotonergic/cholinergic deficits. Embryonic raphe cells (E14) were transplanted into the hippocampus of serotonin-depleted rats. Two to 3 months after transplantation, control, lesioned and grafted rats were tested in a spatial memory task (a water maze) with and without the addition of atropine. All 3 groups could negotiate the water maze equally well, in non-drug conditions. The injection of atropine caused a severe disruption of performance only in the serotonin depleted rats. The presence of an active serotonergic graft was examined in the intact rat hippocampus using the serotonin releasing drug fenfluramine (FFA). A pronounced depression of hippocampal EEG was observed in control and grafted but not in lesioned rats 15 min after the injection of FFA. These results suggest the involvement of serotonin in cognitive functions in the rat. Furthermore, it is suggested that an interaction between serotonergic and cholinergic neurotransmission occurs in the hippocampus.

Animals↗
PubMed1989

Spatial performance is severely impaired in rats with combined reduction of serotonergic and cholinergic transmission.

A possible interaction between serotonergic and cholinergic neurotransmission was examined in relation to the performance of a spatial memory task. Blockade of cholinergic transmission with a high dose of atropine was sufficient to impair performance of a water maze task. A partial reduction of cholinergic transmission using a low dose of atropine had no effect on this performance. Reducing serotonin synthesis, using a specific inhibitor of tryptophane hydroxylase p-chlorophenylalanine (PCPA) also had no effect on performance of such a task. However, a combined treatment with a low dose of atropine and PCPA severely impaired the performance of rats in the water maze. The rats were impaired in both acquisition of the initial spatial task and in reacquisition of a new spatial position (= working memory). These findings suggest an interaction between cholinergic and serotonergic transmission in acquisition and retention of spatial information. Furthermore they propose that deficits in cognitive abilities, observed in aging or Alzheimer's disease, may result from the combined reduction in cholinergic and serotonergic transmission.

Acetylcholine↗
PubMed1988

Serotonin releasers modulate reactivity of the rat hippocampus to afferent stimulation.

Electrical stimulation of the perforant path produces a characteristic population EPSP and population spike in the dentate gyrus of the anesthetized rat. Parenteral administration of a serotonin releasing drug D-fenfluramine (FFA) caused a marked (30-100%) and highly significant increase in dentate gyrus population spike response to perforant path stimulation without affecting the slope of the population excitatory postsynaptic potential (EPSP). This indicates that FFA modifies granular cell excitability to afferent stimulation. The facilitatory effect of FFA was not present in rats depleted of serotonin following treatment with the synthesis inhibitor p-chlorophenylalanine (PCPA) but was restored after restoration of serotonin synthesis with the precursor 5-hydroxytryptophan indicating that presence of serotonin in terminals is required for the action of FFA.

Afferent Pathways↗
PubMedDate not supplied

Effect of 5-hydroxytryptophane on behavior and hippocampal physiology in young and old rats.

Spatial memory ability, tested in a water maze, was severely impaired in control, 24-month-old hooded rats. A daily injection of the serotonin precursor, 5-hydroxytryptophane (5-HTP), prior to training sessions, had no effect on the behavior of the young rats but improved considerably the performance of the old rats in the watermaze. In the same groups of young and aged rats, the response properties of the hippocampal dentate gyrus to perforant path stimulation was assessed before and after parenteral administration of 5-HTP. The dentate gyrus of aged rats produces a smaller EPSPs in response to perforant path stimulation but a larger population spike for a given EPSP than that produced in young rat brains. These differences are not affected by 5-HTP. In young brains, priming commissural stimulation suppresses subsequent reactivity to perforant path stimulation. This priming effect is nearly absent in aged rat hippocampus but reappears when the rat is injected with 5-HTP. It is suggested that the serotonergic innervation of the rat hippocampus plays a major role in regulation of the excitability of the hippocampus and in behavioral functions associated with this structure.

5-Hydroxytryptophan↗
PubMedDate not supplied

Short-term behavioral and electrophysiological consequences of underwater trauma.

In a previous work we found that a 30-s underwater trauma, following 8 days of training for a spatial memory task in the water maze, resulted in poor performance in the spatial memory task at both 1 h and 3 weeks after the trauma. Here we found that compared with naive animals and animals that were trained for the spatial learning task but were not traumatized, the traumatized rats showed impaired performance in a spatial learning task in the water maze 20 min after the trauma and a reduced level of dentate gyrus long-term potentiation (LTP) 40 min after high-frequency stimulation to the perforant path. We also found a positive correlation between the behavioral performance and hippocampal plasticity. The reduced ability to induce LTP suggests that the trauma-related behavioral impairment is mediated by hippocampal-dependent processes. The underwater trauma may provide an important and potentially powerful model for understanding the mechanisms underlying the relationship between stress, cognition, and learning.

Animals↗
PubMedDate not supplied

Spatial training and high-frequency stimulation engage a common pathway to enhance glutamate release in the hippocampus.

We have measured depolarization-induced release of endogenous glutamate in synaptosomes prepared from the dentate gyrus after the induction of LTP by high-frequency stimulation in anesthetized rats, and after training in the water maze. Both spatial training and LTP in untrained rats were accompanied by an increase in glutamate release from dentate synaptosomes. The enhancement of synaptosomal glutamate release induced by high-frequency stimulation was abolished in well-trained rats, and was reduced in partially trained rats and in rats trained in a nonspatial task. However, the magnitude of LTP was similar in well-trained and untrained groups. These results indicate that spatial training activates a glutamate release pathway that converges with that activated in LTP, and demonstrate an unexpected dissociation between increased glutamate release and LTP.

Animals↗
PubMedDate not supplied

Amygdala-hippocampus dynamic interaction in relation to memory.

Typically the term "memory" refers to the ability to consciously remember past experiences or previously learned information. This kind of memory is considered to be dependent upon the hippocampal system. However, our emotional state seems to considerably affect the way in which we retain information and the accuracy with which the retention occurs. The amygdala is the most notably involved brain structure in emotional responses and the formation of emotional memories. In this review we describe a system, composed of the amygdala and the hippocampus, that acts synergistically to form long-term memories of significantly emotional events. These brain structures are activated following an emotional event and cross-talk with each other in the process of consolidation. This dual activation of the amygdala and the hippocampus and the dynamics between them may be what gives emotionally based memories their uniqueness.

Amphetamines↗
PubMedDate not supplied

Serotonin, aging and cognitive functions of the hippocampus.

The cholinergic hypothesis of senile dementia /18/ does not provide a sufficient explanation for age-dependent spatial learning deficits; these are observed before an appreciable reduction of cholinergic markers can be detected. Behavioral deficits similar to those observed in old rats cannot be induced in young rats by comparable cholinergic lesions but do occur following combined cholinergic/serotonergic lesions. Serotonergic raphe grafts in the hippocampus (but not in the entorhinal cortex or hypothalamus) prevent such combined lesion-induced spatial learning deficits. The behavioral deficits are associated with a reduction of hippocampal commissure feed-forward inhibition. Similar reduced inhibition is found in old rats, deficient in their performance of a spatial learning water-maze task. Finally, treating old rats with the serotonergic precursor 5-hydroxytryptophan (5-HTP) reduces the age-dependent spatial learning deficits and restores hippocampal commissure feed-forward inhibition. Serotonin may act in parallel to the cholinergic innervation of the hippocampus by affecting inhibitory interneurons but in addition it may act by modulating acetylcholine release. Acetylcholine release is modulated by serotonin and the enhancing effects of serotonin releasing drugs on dentate granule cell excitability are mediated by acetylcholine. We thus propose that a reduction of serotonergic modulation of hippocampal interneuron activity and impaired modulation of cholinergic effects in the hippocampus contribute to age-dependent cognitive deficits.

Aging↗