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R M Pico

Publications and source records attributed to R M Pico.

14 recordsLinked to original sources
PubMed1994

Ultrastructural plasticity of the dentate gyrus granule cells following recurrent limbic seizures: I. Increase in somatic spines.

Various paradigms have been used to assess the capacity of the adult brain to undergo activity-dependent morphological plasticity. In this report we have employed recurrent limbic seizures as a means of studying the effects of this form of enhanced neuronal activity on cellular morphology and, in particular, on the incidence of somatic spines on the dentate gyrus granule cells. Seizure activity was induced by the placement of focal, unilateral electrolytic lesions in the dentate gyrus hilus of adult rats. At various intervals postlesion, rats with behaviorally verified seizures were sacrificed, and the hippocampi contralateral to the lesions were removed and prepared for electron microscopy. Quantitative analysis showed that as early as 5 hours postlesion there was a dramatic increase in the density and morphological complexity of spines on the perikarya of the granule cells in rats that received seizure-producing hilus lesions when compared to granule cells from control rats. Many of the somatic spines received asymmetric synapses. The increase in somatic spines was dependent on seizure activity and persisted for at least 1 month following a single recurrent seizure episode. CA1 pyramidal neurons, which exhibit changes in gene expression in response to hilus lesion-induced seizures but do not normally possess somatic spines, did not exhibit an activity-dependent elaboration of somatic spines. Thus, the seizure-induced elaboration of somatic spines represents an amplification of an existing feature of the granule cells and not an effect occurring throughout hippocampus. These data provide evidence for very rapid and long-lasting structural plasticity in response to brief episodes of seizure activity in the adult brain.

Animals↗
PubMed1994

Hippocampal epileptogenesis produced by electrolytic iron deposition in the rat dentate gyrus.

Anodal current passed through a stainless-steel electrode, positioned unilaterally in the rat dentate gyrus hilus, will produce recurrent motor seizures and significant changes in the neuronal expression of several messenger RNAs (mRNAs) throughout the full bilateral extent of the hippocampus. The present study quantitatively analyzed electroencephalograms (EEGs) from rats receiving this electrolytic treatment in order to characterize the resultant hippocampal seizure activity. To examine the epileptogenic role of ferric ion deposition to that of current-induced tissue destruction, we compared steel to platinum electrodes. Adult male rats were surgically implanted with a chronic recording electrode in the CA3 region of the hippocampus, and then (contralaterally) with either an insulated steel electrode in the hilus, platinum electrode in the hilus, or steel electrode in the medial entorhinal cortex. Each rat received an anodal current through the nonrecording treatment electrode while connected to a polygraph. Currents ranged from 0.8 mA, 7 s for hilus electrodes to 2.0 mA, 20 s for entorhinal cortex electrodes. EEGs were collected from alert, unrestrained rats for up to 50 consecutive hours, and additional EEGs were recorded periodically over a 4-day period. Subjects were sacrificed and brain sections were microscopically examined for evidence of neuropathology. The results demonstrate that electrolytic deposition of iron ions in the hilus, and not merely hilus tissue destruction, produce electrographic seizure activity within 1-2 h of current passage. Seizures recurred most intensely for 2-3 h, and sporadic epileptiform activity was detected for up to 12 h. Motor seizures of class 4 or 5 were observed in all seizing rats, and were always coincident with hippocampal seizure discharges. Histological examination of brain sections from all subjects found no evidence of cell death in the contralateral hippocampus. The dentate gyrus appeared to be the most epileptogenic site tested because hippocampal iron deposition that did not include the dentate gyrus, or iron deposition in the entorhinal cortex, was significantly less epileptogenic.

Animals↗
PubMed1989

Continuities between outer nuclear membrane and the rough endoplasmic reticulum increase in hippocampal neurons during seizure-induced protein synthesis.

The ultrastructure of rat dentate gyrus granule cells was examined during, and near the termination of, a period of lesion-induced recurrent limbic seizure activity which has previously been demonstrated to stimulate dramatic changes in the biosynthetic activities of these neurons. In animals sacrificed 5 h postlesion (or 3.5 h following seizure onset) the rough endoplasmic reticulum (RER) appeared more extensive than in controls and there was a large, statistically significant increase in the number of continuities between the RER and the outer nuclear membrane (ONM). By 11 h postlesion the latter index had returned to control values although the presence of numerous elevations of the ONM lying in close proximity to free segments of RER was considered indicative of recent dissolution of contact. These data demonstrate modifications in the arrangement of organelles involved in protein synthesis during a period in which the patterns of synthesis by the granule cells are changing but which do not persist through the full period of seizure-induced alterations in synthetic activity.

Animals↗
PubMed1988

Focal hippocampal lesions induce seizures and long-lasting changes in mossy fiber enkephalin and CCK immunoreactivity.

Electrolytic lesions of the dentate gyrus hilus have been demonstrated to induce behavioral seizure activity and to result in perturbations in the amount of enkephalin, cholecystokinin, and dynorphin immunoreactivity in the hippocampal mossy fiber system. In the present study, electroencephalographic (EEG) recordings, made from hippocampus contralateral to a hilus lesion in mouse, demonstrate the presence of recurrent hippocampal seizure activity which begins approximately one hour postlesion and continues for several hours thereafter. Behavioral seizures were found to correspond to periods of epileptiform hippocampal EEG. Immunocytochemical analyses of enkephalin-(ENK-I) and cholecystokinin-immunoreactivity (CCK-I) in contralateral hippocampus of animals sacrificed at various postlesion intervals revealed that both ENK-I and CCK-I were depleted from the mossy fibers at 6 and 12 hr postlesion, and that ENK-I rebounded to supranormal levels by 27 hr. In two animals sacrificed 60 days following lesions which induced extreme behavioral seizure activity, ENK-I was still elevated while CCK-I was completely absent from the mossy fiber system. These data suggest that heightened physiological activity, in the form of recurrent limbic seizures, induces long-lasting but quite different alterations in enkephalin and CCK concentration in the hippocampal mossy fiber system.

Afferent Pathways↗
PubMed1987

A tripeptide protease inhibitor attenuates conditioned avoidance behavior.

In a single 10-s training trial, hatchling chicks were conditioned to suppress their spontaneous peck response to a small spherical target by coating it with an aversive liquid. A 24-h test trial employing a dry target demonstrated a robust memory for the training manifested in passive avoidance behavior. Leupeptin, a low-molecular-weight antiprotease, injected i.c.v. 1 h or 15 min prior to training attenuated the long-term avoidance response but not the initial training-induced peck suppression. Leupeptin had no effect on memory if given posttraining. A dose response experiment revealed that a 100- or 200-micrograms dose of leupeptin reliably impaired conditioned avoidance, whereas a 25 or 50-micrograms dose was ineffective. A dipeptide leupeptin analog (L-leucyl-L-arginine) possessed one-half the potency of the tripeptide in the memory task, and a different protease inhibitor (aprotinin) failed to effect the conditioned avoidance behavior. The mechanisms by which leupeptin may exert its influence in this behavioral paradigm and others are discussed.

Animals↗
PubMed1987

Differences in learning between hyperprolinemic mice and their congenic controls.

These experiments expanded earlier work on hyperprolinemic mice which showed learning deficits. The following behavioral tasks were used: step-through, passive avoidance; T-maze acquisition; shuttlebox acquisition, and radial-arm maze. Mouse species included PRO/Re-bb (genetically hyperprolinemic mice) and PRO/Re-aa (congenic nonhyperprolinemic controls) obtained from the Jackson Breeding Laboratories. Hyperprolinemic mice were impaired in acquiring T-maze and shuttlebox footshock avoidance behavior. One-trial passive avoidance behavior did not clearly differentiate between the groups. Radial maze performance was poor in both groups due possibly to observed acrophobia and lack of exploratory behavior. The results of this study combined with previously published work suggest that high-brain proline in conjunction with other amino acid changes account for the learning deficits.

Amino Acid Metabolism, Inborn Errors↗
PubMed1985

During stepwise cue deletion, rat place behaviors correlate with place unit responses.

The place behaviors of intact rats, and of those receiving fornix lesions, were examined in the radial-arm maze. A cue-restricted environment was constructed wherein the location of arms with food rewards were identifiable only by their position in relation to an intermittently rotated 4-cue set. Food obtainment was measured during a procedure in which either 1, 2 or 3 of the cues were removed during a block of test sessions. Control animals demonstrated place navigation abilities robust to the deletion of any 1 or 2 cues. The performance of lesioned rats declined in a manner consistent with the number of absent stimuli. The results indicate that the behavioral expressions of place knowledge relate to the responsiveness of hippocampal place cells.

Animals↗
PubMed1984

The radial maze performance of mice: assessing the dimensional requirements for serial order memory in animals.

Two versions of the eight-arm radial maze were used to test the working memory abilities of CD-1 mice. In an elevated open-arm radial maze, mice quickly and successfully learned the multiple-choice procedure. However, mice trained in an enclosed-arm radial maze mastered the task only by developing a kinesthetic strategy of response. When a delay was imposed between choices 4 and 5, mice in the open-arm radial maze retained high performance levels. Choice accuracy declined markedly for mice in the enclosed-arm radial maze under delay conditions. Transference of the two groups of mice between the two mazes resulted in a complete reversal of sampling strategies. Minor changes to the enclosed-arm maze and room illumination permitted mice to successfully perform in the non-egocentric manner which they exclusively employed in the open-arm maze. The results show that mice can demonstrate a working memory capacity when in an environmentally adequate radial maze, and provide evidence against the existence of nonspatial working memory ability. The discussion examines the procedural and environmental requirements for displays of working memory, and a set of hypotheses is presented which serve to integrate the working memory and cognitive mapping theories.

Animals↗
PubMed1983

Dose-dependent and time-dependent action of oxytocin on chick memory.

Experiments were conducted to investigate the dose-related and time-dependent effects of oxytocin on memory for a one-trial conditioned taste aversion task using two-day old chicks. Oxytocin was administered intracerebrally 1 min posttraining to 5 groups of chicks in dose levels differing by a factor of 10 and ranging from 5.0 pg to 50 ng. A second experiment tested the time-dependent nature of the neuropeptide's action. In this experiment the oxytocin (5.0 ng) was administered at either 1 min, 9 min or 59 min posttraining. In both experiments saline-injected control groups were included. The taste aversion training for all experiments consisted of presenting an attractive lure, coated with an aversive liquid (EtOH), to each chick for a 10-s training trial. Most chicks pecked 1 or 2 times at the lure before inhibiting any further response. The retention testing took place 24 h after the training and consisted of presenting the dry, uncoated lure to each chick for an additional 10 s. Chicks that avoided pecking at the lure were considered to have exhibited enhanced retention. The groups of chicks receiving 50 pg to 50 ng of oxytocin exhibited enhancement of retention, as did the 1 min group of the time-dependent experiment. These results are compared to the effects on memory consolidation in chicks induced by vasopressin and L-prolyl-L-leucyl-glycineamide. The apparent conflict between these results and those obtained in mammalian studies with oxytocin are discussed.

Animals↗
PubMed1983

Brain glutamate inhibition and amnesia: evidence provided by proline analog action.

The action of proline and its analog as glutamate antagonists was investigated in CNS tissue of the neonatal chick. Avian brain slices were incubated in low concentrations of L-proline, D-proline, DL-3,4-dehydro-proline, L-prolyl-L-proline, or in avian physiological salt solution before depolarization was induced by application of 45 mM K+. Glutamate was determined in the efflux material collected both before and after tissue stimulation. The release of endogenous glutamate was inhibited significantly by exposure to L-proline, DL-3,4-dehydroproline and L-prolyl-L-proline. The degree of glutamate inhibition correlated with the amnestic potency of these substances. The manner in which these results strengthen the hypothesis of glutamate involvement in memory processes is discussed.

Amnesia↗
PubMed1982

Memory enhancement induced in chicks by L-prolyl-L-leucyl-glycinamide.

Two-day-old chicks were injected either intraventricularly or intraperitoneally with saline or a L-prolyl-L-leucyl-glycinamide solution. This C-terminal tripeptide of oxytocin produced retrograde enhancement when injected centrally but not peripherally. Possible memory mechanisms are discussed in light of this peptide's relationship to oxytocin, MSH, and dopaminergic systems.

Animals↗
PubMedDate not supplied

L-prolyl-L-arginyl-glycineamide induces memory enhancement in chicks.

Two-day-old chicks were injected either intraventricularly or intraperitoneally with saline or a L-prolyl-L-arginyl-glycineamide solution. This C-terminal tripeptide of arginine vasopressin produced dose dependent enhancement effects when injected centrally but not peripherally. Physical debilitation and/or aversive effects of the peptide were eliminated as the cause of the decreased responding noted in memory enhancement studies using this avoidance paradigm. Possible memory mechanisms are discussed in light of this peptide's relationship to vasopressin, vasotocin, and L-propyl-L-leucyl-glycineamide.

Analysis of Variance↗
PubMedDate not supplied

Arginine vasotocin delays extinction of a conditioned avoidance behavior in neonatal chicks.

One minute after single-trial avoidance conditioning, young cockerels received intracerebroventricular or intraperitoneal injections of saline or arginine vasotocin (dose range: 0.004 to 16 micrograms/chick). Retroactive enhancement of the learned response was observed 24 hours post-training for some dose levels, but not for others. A 0.4 micrograms vasotocin dose also delayed extinction when injected 9 minutes after training. Behavioral similarities between avian and mammalian responses to vasotocin and other neuroactive peptides are discussed.

Animals↗