Disruption of hippocampal rhythms via optogenetic stimulation during the critical period for memory development impairs spatial cognition

Autor: Michelle L. Kloc, Francisco Velasquez, Rhys W. Niedecker, Jeremy M. Barry, Gregory L. Holmes
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Brain Stimulation, Vol 13, Iss 6, Pp 1535-1547 (2020)
Druh dokumentu: article
ISSN: 1935-861X
DOI: 10.1016/j.brs.2020.08.011
Popis: Background: Hippocampal oscillations play a critical role in the ontogeny of allocentric memory in rodents. During the critical period for memory development, hippocampal theta is the driving force behind the temporal coordination of neuronal ensembles underpinning spatial memory. While known that hippocampal oscillations are necessary for normal spatial cognition, whether disrupted hippocampal oscillatory activity during the critical period impairs long-term spatial memory is unknown. Here we investigated whether disruption of normal hippocampal rhythms during the critical period have enduring effects on allocentric memory in rodents. Objective/hypothesis: We hypothesized that disruption of hippocampal oscillations via artificial regulation of the medial septum during the critical period for memory development results in long-standing deficits in spatial cognition. Methods: After demonstrating that pan-neuronal medial septum (MS) optogenetic stimulation (465 nm activated) regulated hippocampal oscillations in weanling rats we used a random pattern of stimulation frequencies to disrupt hippocampal theta rhythms for either 1Hr or 5hr a day between postnatal (P) days 21–25. Non-stimulated and yellow light-stimulated (590 nm) rats served as controls. At P50-60 all rats were tested for spatial cognition in the active avoidance task. Rats were then sacrificed, and the MS and hippocampus assessed for cell loss. Power spectrum density of the MS and hippocampus, coherences and voltage correlations between MS and hippocampus were evaluated at baseline for a range of stimulation frequencies from 0.5 to 110 Hz and during disruptive hippocampal stimulation. Unpaired t-tests and ANOVA were used to compare oscillatory parameters, behavior and cell density in all animals. Results: Non-selective optogenetic stimulation of the MS in P21 rats resulted in precise regulation of hippocampal oscillations with 1:1 entrainment between stimulation frequency (0.5–110 Hz) and hippocampal local field potentials. Across bandwidths MS stimulation increased power, coherence and voltage correlation at all frequencies whereas the disruptive stimulation increased power and reduced coherence and voltage correlations with most statistical measures highly significant (p
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