Search bioRxiv⌕ Search

Biology subjects

Mizrahi-Kliger, A.

Publications and source records attributed to Mizrahi-Kliger, A..

2 recordsLinked to original sources

Sleep to forget: active control of consolidation and forgetting by slow-wave sleep dynamics

Sleep supports both the consolidation of new memories and the forgetting of others, but how the cortex flexibly controls these outcomes remains poorly understood. Recent work has shown that two types of Up states may play distinct, competing roles during slow-wave sleep (SWS): slow waves actively consolidate memory traces, whereas delta waves promote their weakening. Here we use a biophysical thalamocortical network model equipped with spike-timing-dependent plasticity to investigate the synaptic mechanisms underlying this dissociation. By manipulating the intrinsic Ca2+ dynamics of cortical pyramidal cells, we generate both slow and delta wave Up states within a single network. Using a sequence-learning task paradigm we recapitulate the optogenetic dissociation: removing plasticity during slow waves degrades the memory, while removing it during delta waves enhances consolidation. Mechanistically, the model reveals the longer slow wave Up state affords a spontaneous reactivation phase, occurring after the interfering input, during which the trained memory is selectively reactivated and protected, a phase the truncated delta Up state cannot support. We further find that delta waves sparsen the synaptic representation more than slow waves and predict that the balance between consolidation and forgetting can be flexibly tuned by the ratio of slow to delta waves during SWS.

neuroscience↗

Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons

The tonic activity of striatal cholinergic interneurons (CINs) is modified differentially by their afferent inputs. Although their unitary synaptic currents are identical, in most CINs cortical inputs onto distal dendrites only weakly entrain them, whereas proximal thalamic inputs trigger abrupt pauses in discharge in response to salient external stimuli. To test whether the dendritic expression of the active conductances that drive autonomous discharge contribute to the CINs capacity to dissociate cortical from thalamic inputs, we used an optogenetics-based method to quantify dendritic excitability. We found that the persistent sodium (NaP) current gave rise to dendritic boosting, and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) current gave rise to a subhertz membrane resonance. This resonance may underlie our novel finding of an association between CIN pauses and internally-generated slow wave events in sleeping non-human primates. Moreover, our method indicated that dendritic NaP and HCN currents were preferentially expressed in proximal dendrites. We validated the non-uniform distribution of NaP currents pharmacologically; with two-photon imaging of dendritic back-propagating action potentials; and by demonstrating boosting of thalamic, but not cortical, inputs by NaP currents. Thus, the localization of active dendritic conductances in CIN dendrites mirrors the spatial distribution of afferent terminals and may promote their differential responses to thalamic vs. cortical inputs.

neuroscience↗