Biology subjects

Hartwich, K.

Publications and source records attributed to Hartwich, K..

3 recordsLinked to original sources

bioRxiv2023

Offline hippocampal reactivation during dentate spikes supports flexible memory

Stabilizing new memories requires coordinated neuronal spiking activity during sleep. Hippocampal sharp-wave ripples (SWRs) in the Cornu Ammonis (CA) region, and dentate spikes (DSs) in the dentate gyrus (DG) are prime candidate network events supporting this offline process. SWRs have been studied extensively but the contribution of DSs remains unclear. By combining triple-(DG-CA3-CA1) ensemble recordings and closed-loop optogenetics in mice we show that, like SWRs, DSs synchronize spiking across DG and CA principal cells to reactivate population-level patterns of neuronal coactivity expressed during prior waking experience. Notably, the population coactivity structure in DSs is more diverse and higher-dimensional than that seen during SWRs. Importantly, suppressing DG granule cell spiking selectively during DSs impairs subsequent flexible memory performance in a multi-object recognition task and associated hippocampal patterns of neuronal coactivity. We conclude that DSs constitute a second offline network event central to hippocampal population dynamics serving memory-guided behavior.

neuroscience↗

bioRxiv2023

Organizing the coactivity structure of the hippocampus from robust to flexible memory

New memories are integrated into prior knowledge of the world. But what if consecutive memories exert opposing demands on the host brain network? We report that acquiring a robust (food-context) memory constrains the hippocampus within a population activity space of highly correlated spike trains that prevents subsequent computation of a flexible (object-location) memory. This densely correlated firing structure developed over repeated mnemonic experience, gradually coupling neurons of the superficial CA1 pyramidale sublayer to whole population activity. Applying hippocampal theta-driven closed-loop optogenetic suppression to mitigate this neuronal recruitment during (food-context) memory formation relaxed the topological constraint on hippocampal coactivity and restored subsequent flexible (object-location) memory. These findings uncover an organizational principle for the peer-to-peer coactivity structure of the hippocampal cell population to successfully meet memory demands.

neuroscience↗

bioRxiv2021

Consequences of human Tau aggregation in the hippocampal formation of ageing mice in vivo

Intracellular aggregation of hyperphosphorylated Tau (pTau) in the brain is associated with cognitive and motor impairments, and ultimately neurodegeneration. We investigate how human pTau affects cells and network activity in the hippocampal formation of THY-Tau22 tauopathy model mice in vivo. We find that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to neurodegeneration, and we establish that pTau spreads to oligodendrocytes. During goal-directed virtual navigation in aged transgenic mice, we detect fewer high-firing prosubicular pyramidal cells but the firing population retains its coupling to theta oscillations. Analysis of network oscillations and firing patterns of pyramidal and GABAergic neurons recorded in head-fixed and freely-moving mice suggests preserved neuronal coordination. In spatial memory tests, transgenic mice have reduced short-term familiarity but spatial working and reference memory are surprisingly normal. We hypothesize that unimpaired subcortical network mechanisms maintain cortical neuronal coordination, counteracting the widespread pTau aggregation, loss of high-firing cells, and neurodegeneration.

neuroscience↗