Ensemble activity and behavior: what's the code?
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Action Potentials↗
Biomedical subjects
R E Hampson
Publications and source records attributed to R E Hampson.
Cannabinoids modulate voltage sensitive potassium A-current in hippocampal neurons via a cAMP-dependent process.
Previous studies have shown that cannabinoid receptor analogs increase voltage-dependent potassium A-current (IA) in cultured hippocampal cells. Because cannabinoid receptors inhibit adenylate cyclase, the present study explored whether cAMP played a role in mediating this effect on IA. The specific issue of whether cannabinoid receptor modulation of voltage-dependent IA acts via a cAMP-dependent process was investigated. The cAMP analog, 8-bromo-cAMP, as well as the adenylate cyclase stimulant forskolin, produced concentration-dependent shifts in IA that were opposite those produced by cannabinoid receptor ligands. Moreover, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also produced a marked negative shift in the steady-state voltage dependence of IA and increased the effect of forskolin on IA. As shown in previous studies, the cannabinoid agonist WIN 55,212-2 increased IA via a decrease in steady-state voltage-dependent inactivation of IA. WIN 55,212-2 also reversed the effects of forskolin on IA. The electrophysiological studies were paralleled by direct assays of cAMP in these cells, where cannabinoids inhibited forskolin-stimulated cAMP by 50% in a pertussis toxin-sensitive manner. The results confirmed that pertussis toxin-sensitive cannabinoid receptor-mediated changes in IA were probably the result of inhibition of adenylate cyclase. The findings are discussed in terms of modulation of IA conductance properties via cannabinoid receptor-mediated inhibition of cAMP levels within the cell.
1-Methyl-3-isobutylxanthine↗
Information processing in the dentate gyrus.
The dentate gyrus is viewed as playing a major role in the generation of epileptiform activity. The ramifications of disrupted neuronal activity in the dentate gyrus are discussed with emphasis on the role of the dentate gyrus in processing sensory information. Several features of conditioned auditory-evoked potentials reflective of activity in the perforant path are described with respect to the activity of dentate granule cells. Comparisons of the sequential changes which occur in the perforant path synaptic activity and dentate granule cell discharge reveal an inverse relationship between synaptic input from the perforant path and degree of cell firing on any given trial. This inverse relationship is addressed in terms of extra-hippocampal projections to the cortex as well as recurrent connections to the enthorhinal area and the cells of origin of the perforant path. It is concluded that the perforant path regulates the response of the dentate granule cells to sensory input from the neocortex by decreasing synaptic drive when granule cell activity is high and increasing that synaptic drive when granule cell activity is low. This extra-hippocampal control of perforant path activity serves to 'clamp' the dentate granule cell response rate within a tightly controlled range to guarantee that granule cells will have some response capacity to 'unexpected' sensory experiences.
Afferent Pathways↗
The effects of delta-9-THC on mechanisms of learning and memory.
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Animals↗
Effects of delta-9-tetrahydrocannabinol on sensory evoked hippocampal activity in the rat: principal components analysis and sequential dependency.
The effects of delta-9-tetrahydrocannabinol (delta-9-THC) were assessed on identified hippocampal sensory evoked potentials obtained from rats during performance of a two-tone discrimination task. Techniques which analyzed the trial-to-trial sequential and serial dependence underlying the variance in evoked potential amplitude were utilized. Waveforms of averaged tone-evoked potentials (AEPs) recorded from the outer molecular layer of the dentate gyrus (OM) were subjected to principal components analysis which revealed eight principal components accounting for 90.3% of the total variance in the set of OM AEP waveforms. Five of the eight components were altered significantly in comparison to vehicle injection sessions after administration of either a 1.0- or 2.0-mg/kg dose of delta-9-THC. These alterations accounted for the amplitude and latency changes in the OM AEP described in a previous report. In addition, delta-9-THC also disrupted the trial-to-trial sequential dependency of the OM AEPs. An important result showed that delta-9-THC selectively influenced the serial dependence of the OM AEP. These results implicate delta-9-THC as a potent disruptor of temporally specific information as it is processed by the hippocampus and suggest that such disruption may be the basis of delta-9-THC effects on memory processes in humans.
Animals↗
Hippocampal place cells: stereotypy and plasticity.
Hippocampal complex spike cells were recorded during exploration for water delivered to cups located in various regions of an elevated platform. Place fields were recorded with a video monitoring system that recorded movements as the animal explored each of the 5 cup locations where water was delivered on the platform. Plasticity of place cell firing as a function of selective water delivery to specific cup locations on the platform was also examined. Several characteristics of place cell firing were studied that indicated a high degree of control by factors such as relative direction of movement and trajectory through the field. Time-shift analyses indicated cell firing was most representative of the place field at the time of spike occurrence. It was demonstrated that place fields possess borders in which firing was increased or decreased upon entering or leaving a particular region of the platform. The most important finding from this investigation was the pronounced degree of plasticity exhibited by place cells. Selective delivery of water to a single location on the platform was sufficient in most of the cases tested to shift the location of the field to the location where water was available. These findings suggest hippocampal place cell firing, although highly influenced by spatial and directional features of the environment, can readily change under conditions in which significant stimuli are added or removed from those locations.
Animals↗
Control of sensory activation of granule cells in the fascia dentata by extrinsic afferents: septal and entorhinal inputs.
Three groups of rats were trained to perform a differential discrimination task in a 2-tone operant conditioning paradigm. One group received electrolytic lesions of the medial septal nuclei, another received electrolytic or knife cut lesions of the entorhinal cortex. These groups were compared with a normal control group. Recordings of granule cells in the fascia dentata were obtained in all animals during criterion performance of the behavioral task. Both lesions produced disruption of behavioral discrimination in the form of increased error and intertrial responding. Granule cell discharges to the tone stimuli were disrupted by each type of lesion. Septal lesions reduced the differential discharge tendency to CS+ and CS- and changed granule cell firing on all trials to statistically resemble firing on CS- trials in normal animals. Extensive lesions in the entorhinal cortex or knife cuts that severed the perforant path caused near elimination of the tone-evoked discharges to both the CS+ and CS-tones. Septal and entorhinal lesions caused marked changes in the sequential dependence of the granule cell discharge compared with intact animals. Results are discussed in terms of the control of the granule cell discharge by the remaining afferent pathways in each type of lesion condition.
Acoustic Stimulation↗
Sequential dependencies regulate sensory evoked responses of single units in the rat hippocampus.
Unit activity from 3 major types of hippocampal cells were recorded from the CA1, CA3 and dentate granule cell layers of the hippocampus in awake freely moving rats. Units were classified as complex spike (ComSp), theta and dentate granule cells (G-cell) based on their spontaneous and stimulus-evoked firing characteristics. Single trial records for each cell type were collected during criterion performance of a two-tone discrimination task. Results showed that: tone-evoked discharges of theta- and G-cells, but not ComSp cells, were influenced by the reward status of the tone presented; the firing tendency of all cell types was significantly influenced by the preceding trial sequence; different types of preceding trial sequences including single and double alternation and runs of positive or negative trials significantly affected the firing tendency of all 3 cell types; the pattern of theta- and G-cell discharges differed with respect to latency to peak discharge and the duration of the discharge following long runs of similar trials. These effects were similar to previously described sequential influence on synaptically identified sensory evoked potentials in the dentate gyrus.
Acoustic Stimulation↗
Processing of sensory information in the hippocampus.
The functional significance of the mammalian hippocampal formation is considered within the context of specific neural circuits responsible for the processing of sensory information. The anatomic and physiologic features of the major input pathways from the hypothalamus, septum, and entorhinal cortex are reviewed with regard to sensory activation of hippocampal cell fields. A model is presented which interrelates the functional plasticity of hippocampal synaptic processes to reciprocal connections between input and output pathways. The manner in which sensory responsiveness is modulated in the rat dentate gyrus as a function of both cognitive and behavioral factors is described. The hippocampus is discussed with respect to its role as a short-term item-specific store of behaviorally relevant sensory information.
Animals↗
delta 9-Tetrahydrocannabinol differentially affects sensory-evoked potentials in the rat dentate gyrus.
The effects of low doses of delta 9-tetrahydrocannabinol (THC) on auditory-evoked potentials recorded from the outer molecular layer of the dentate gyrus of the rat hippocampus were assessed during performance of an auditory two-tone discrimination task. Conditioned behavior was disrupted up to 2 hr after i.p. injections of delta 9-THC at 1.0 to 2.0 mg/kg: responses to the rewarded stimulus decreased significantly and latency to respond increased significantly. Concurrent recordings indicated that these same doses of THC did not grossly distort the outer molecular layer averaged evoked potential waveform, but did produce opposing alterations in the amplitudes of the previously studied averaged evoked potential components N1 and N2. The amplitude of the N1 component was decreased significantly 0 to 2 hr after THC injection, whereas the amplitude of the N2 component increased significantly. THC injection at 0.5 mg/kg had no significant effects on performance or on N1 or N2 amplitudes. Recovery from the effects of 1.0 to 2.0 mg/kg of delta 9-THC was essentially complete 2 to 4 hr after injection for both measures of performance and for both N1 and N2 amplitudes. The results demonstrate that low doses of delta 9-THC distort behaviorally relevant sensory information converging on the dentate gyrus and support the hypothesis that the psychoactive effects of marijuana may be mediated by action within the hippocampus.
Animals↗
Effects of delta 9-tetrahydrocannabinol on sensory-evoked discharges of granule cells in the dentate gyrus of behaving rats.
Extracellular action potentials were recorded from identified cells in the dentate gyrus of the awake freely moving rat during performance of a two-tone discrimination task. The effects of low doses of delta 9-tetrahydrocannabinol (delta 9-THC) were assessed on the firing patterns of granule cells to the tone stimuli. Intraperitoneal injections of delta 9-THC at 1.0 and 2.0 mg/kg, but not 0.5 mg/kg, produced a significant suppression of granule cell activity lasting up to 4 hr. This suppression was present in both the spontaneous (pretone) activity and tone-evoked responses of granule cells. The tone responses of cells recorded from the inferior colliculus were unaffected by THC injection at 1.0 and 2.0 mg/kg, implicating further the hippocampus as a site of specific action of delta 9-THC. In the preceding paper it was demonstrated that such doses produced both impairment of discrimination behavior and modifications of sensory-evoked potentials recorded from the dentate gyrus. However, the influence of delta 9-THC on cell firing in the dentate gyrus was more severe both in magnitude and duration of suppression than were the effects on behavior and on sensory-evoked potentials.
Animals↗
Sequence-related changes in sensory-evoked potentials in the dentate gyrus: a mechanism for item-specific short-term information storage in the hippocampus.
Sensory-evoked potentials were recorded from the dentate gyrus of the rat hippocampus during performance of a differential auditory discrimination task. The short latency (20 ms) component (N1) of the sensory-evoked potential showed systematic amplitude fluctuations dependent upon the sequence of positive and negative trials preceding the presentation of a given trial and did not depend on the associated reward values of the individual tone stimuli which evoked the potential. The amplitude fluctuations could be accurately depicted by a model which retained the sequence for the five preceding trials in a "buffer" with exponentially decaying influence as a function of time of trial occurrence within the sequence. The results provide evidence that the hippocampus encodes accurate short-lasting representations of sensory events which can provide the basis for storage of information pertaining to past experiences.
Acoustic Stimulation↗
Effectiveness of detergent and detergent plus bleach for decontaminating pesticide applicator clothing.
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Detergents↗