Biology subjects

Kaganovsky, K.

Publications and source records attributed to Kaganovsky, K..

3 recordsLinked to original sources

bioRxiv2023

Hippocampal place code plasticity in CA1 requires postsynaptic membrane fusion

Rapid delivery of glutamate receptors to the postsynaptic membrane via vesicle fusion is a central component of synaptic plasticity. However, it is unknown how this process supports specific neural computations during behavior. To bridge this gap, we combined conditional genetic deletion of a component of the postsynaptic membrane fusion machinery, Syntaxin3 (Stx3), in hippocampal CA1 neurons of mice with population in vivo calcium imaging. This approach revealed that Stx3 is necessary for forming the neural dynamics that support novelty processing, spatial reward memory and offline memory consolidation. In contrast, CA1 Stx3 was dispensable for maintaining aspects of the neural code that exist presynaptic to CA1 such as representations of context and space. Thus, manipulating postsynaptic membrane fusion identified computations that specifically require synaptic restructuring via membrane trafficking in CA1 and distinguished them from neural representation that could be inherited from upstream brain regions or learned through other mechanisms.

neuroscience↗

bioRxiv2022

Dissociating encoding of memory and salience by manipulating long-term synaptic potentiation

Neural codes are thought to be reorganized during memory formation by long-term potentiation (LTP) of synapses. Here, using a novel approach for selectively blocking LTP, we found that eliminating LTP in hippocampal or striatal circuits only produces limited effects on learning and memory. To reconcile the discrepancy between the large physiological effect of blocking LTP and the absent effect on learning, we studied how LTP impacts neuronal computations in the hippocampus using in-vivo Ca2+-imaging. Contrary to current conceptual frameworks, we found that hippocampal CA1-region LTP is not required for accurate representations of space in hippocampal neurons, but rather endows these neurons with reward- and novelty-coding properties. Thus, instead of driving formation of cognitive maps and memory engrams, CA1-region LTP incorporates salience information into cognitive representations. One-Sentence SummaryA novel approach for studying long-term potentiation reveals its surprising and selective role in salience encoding

neuroscience↗

bioRxiv2018

A conserved nuclear export complex coordinates transcripts for dopaminergic synaptogenesis and neuronal surviva

Synaptic vesicle and active zone proteins are required for synaptogenesis. The molecular mechanisms for coordinated synthesis of these proteins are not understood. Using forward genetic screens, we identified the conserved THO nuclear export Complex (THOC) as master regulator of presynapse development in C.elegans dopaminergic neurons. In THOC mutants, synaptic messenger RNAs are trapped in the nucleus, resulting in dramatic decrease of synaptic protein expression, near complete loss of synapses and compromised dopamine function. cAMP-responsive element binding protein (CREB) interacts with THOC to mark activity-dependent transcripts for efficient nuclear export. Deletion of the THOC subunit Thoc5 in mouse dopaminergic neurons causes severe defects in synapse maintenance and subsequent neuronal death in the Substantia Nigra compacta (SNc). These cellular defects lead to abrogated dopamine release, ataxia and animal death. Together, our results argue that nuclear export mechanisms can select specific mRNAs and be a rate-limiting step for synapse development and neuronal survival.\n\nHighlightsO_LIDopaminergic presynapses are severely impaired in thoc mutant worms and mice\nC_LIO_LITHOC specifically controls the nuclear export of synaptic transcripts\nC_LIO_LICREB recruits THOC onto activity-dependent synaptic transcripts for efficient export\nC_LIO_LIDopamine neurons in the SNc degenerate upon conditional knock-out of thoc5\nC_LI

neuroscience↗