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Aksamaz, S.

Publications and source records attributed to Aksamaz, S..

2 recordsLinked to original sources

Single acoustic closed loop stimulation in mice to modulate hippocampo-thalamo-cortical activity and performance

Neural brain rhythms of sleep reflect neuronal activity underlying sleep-associated memory consolidation. The modulation of brain rhythms, for instance the sleep slow oscillation (SO) is used both to investigate neurophysiological mechanisms as well as to measure the impact on presumed functional correlates. In humans, auditory closed-loop stimulation targeted to the SO Up-state successfully enhanced the slow oscillation rhythm and phase-dependent spindle activity, although effects on memory retention have varied. Here, we aim to disclose relations between stimulation induced hippocampo-thalamo-cortical activity and retention performance on a hippocampus dependent task in mice. Closed-loop acoustic stimuli applied during four SO phases always acutely increased sharp wave ripple (SPWR) activity without disrupting non-rapid eye movement (NREM) sleep. Stimulation achieved an above chance preference index for stimuli delivered across a 3 h retention interval of sleep at the SO Up-state and at the Down-to-Up-state, but not at the Down-state nor late Up-state/Up-to Down-state. Results support the use of closed-loop acoustic stimulation in mice to investigate the inter-regional mechanisms underlying memory consolidation.

neuroscience↗

Schizophrenia-related cognitive dysfunction in the Cyclin-D2 knockout mouse model of ventral hippocampal hyperactivity

Elevated activity at the output stage of the anterior hippocampus has been described as a physiological endophenotype of schizophrenia, and its development maps onto the transition from its prodromal to its psychotic state. Interventions that halt the spreading glutamatergic over-activity in this region and thereby the development of overt schizophrenia could be promising therapies. However, animal models with high construct validity to support such pre-clinical development are scarce. The Cyclin-D2 knockout (CD2-KO) mouse model shows a hippocampal Parvalbumin-interneuron dysfunction and its pattern of hippocampal over-activity shares similarities with that seen in prodromal patients. In a comprehensive phenotyping of CD2-KO mice, we found that they displayed novelty-induced hyperlocomotion (a correlate in the positive symptom domain), that was largely resistant against D1- and D2-dopamine receptor antagonism, but responsive to the mGluR2/3-agonist LY379268. In the negative symptom domain, CD2-KO mice showed transiently reduced sucrose-preference (anhedonia), but enhanced interaction with novel mice and objects, as well as normal nest building and incentive motivation. Also, unconditioned anxiety, perseveration, and motor impulsivity were unaltered. However, in the cognitive domain, CD2-knockouts showed reduced executive function in assays of rule-shift and rule-reversal learning, but also an impairment in working memory, that was resistant against LY379268. In contrast, sustained attention and forms of spatial and object-related memory that are mediated by short-term habituation of stimulus-specific attention were intact. Our results suggest, that CD2-KO mice are a valuable model in translational research targeted at the pharmacoresistant cognitive symptom domain in causal relation to hippocampal over-activity in the prodrome-to-psychosis transition.

animal behavior and cognition↗