Abstract
BackgroundMany sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R) complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity.ResultsUsing an in vitro model of SPW-R activity we found that thiopental (50–200 μM) significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70–430 %). At the concentration of 25 μM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 ± 5%, n = 12, P < 0.01), and suppressed the rhythmicity of SPWs by 43 ± 15% (n = 6, P < 0.05). The drug disrupted the synchrony of SPWs within the CA1 region at 50 μM (by 19 ± 12%; n = 5, P < 0.05). Similar effects of thiopental were observed at higher concentrations. Thiopental did not affect the frequency of ripple oscillation at any of the concentrations tested (10–200 μM). Furthermore, the drug significantly prolonged single SPWs at concentrations ≥50 μM (it increased the half-width and the duration of SPWs by 35–90 %). Thiopental did not affect evoked excitatory synaptic potentials and its results on SPW-R complexes were also observed under blockade of NMDA receptors. Phenobarbital significantly accelerated SPWs at 50 and 100 μM whereas it reduced their rate at 200 and 400 μM. Furthermore, it significantly prolonged SPWs, reduced their synchrony and reduced the quantity of ripples only at the clinically very high concentration of 400 μM, reported to affect memory.ConclusionWe hypothesize that thiopental, by interfering with SPW-R activity, through enhancement of the GABAA receptor-mediated transmission, affects memory processes which involve hippocampal circuit activation. The quantity but not the frequency of ripple oscillation was affected by the drug.
Highlights
Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms
Studies showing temporal correlation between Sharp-wave ripple (SPW-R) and neocortical activity [17,20,21] suggest that sharp waves (SPWs)-R constitute the neuronal substrate for information transfer in the hippocampo-neocortical circuits [22], contributing to the longterm storage of short-term memories and to memory consolidation in neocortical circuits [17,23,24]
Characteristics of SPW-R activity Spontaneous sharp wave-ripple (SPW-R) complexes (Fig. 1A,B) were consistently recorded in seventy-eight ventral hippocampal slices taken from forty-eight animals
Summary
Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Structured activity of cell assemblies is thought to underlie encoding and transient storage of explicit memory traces in the hippocampal circuit [8]. These memory traces are reactivated during subsequent behavioral stages [9,10,11] namely during bursts of activity called sharp waveripple complexes (SPW-R) consisting of a relatively slow wave The study of the effects of amnesia-inducing agents on hippocampal SPW-R activity becomes increasingly interesting in light of the above research evidence
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