Biology subjects

Venance, L.

Publications and source records attributed to Venance, L..

3 recordsLinked to original sources

bioRxiv2018

Actomyosin-mediated nanostructural remodeling of the presynaptic vesicle pool by cannabinoids induces long-term depression

Endo- and exocannabinoids, such as the psychoactive component of marijuana, exert their effects on brain function by inducing several forms of synaptic plasticity through the modulation of presynaptic vesicle release. However, the molecular mechanisms underlying the widely expressed endocannabinoid-mediated long-term depression (eCB-LTD), are poorly understood. Here, we reveal that eCB-LTD depends on the contractile properties of the pre-synaptic actomyosin cytoskeleton. Preventing this contractility, both directly by inhibiting non-muscle myosin II NMII ATPase and indirectly by inhibiting the upstream Rho-associated kinase ROCK, abolished long-term, but not short-term forms of cannabinoid-induced functional plasticity in both inhibitory hippocampal and excitatory cortico-striatal synapses. Furthermore, using 3D superresolution microscopy, we find an actomyosin contractility-dependent redistribution of synaptic vesicle pools within the presynaptic compartment following cannabinoid receptor activation, leading to vesicle clustering and depletion from the pre-synaptic active zone. These results suggest that cannabinoid-induced functional plasticity is mediated by a nanoscale structural reorganization of the presynaptic compartment produced by actomyosin contraction. By introducing the contractile NMII as an important actin binding/structuring protein in the dynamic regulation of synaptic function, our results open new perspectives in the understanding of mechanisms of synaptic and cognitive function, marijuana intoxication and psychiatric pathogenesis.

neuroscience↗

bioRxiv2018

Encoding of odor fear memories in the mouse olfactory cortex

Odor memories are exceptionally robust and essential for animal survival. The olfactory (piriform) cortex has long been hypothesized to encode odor memories, yet the cellular substrates for olfactory learning and memory remain unknown. Here, using intersectional, cFos-based genetic manipulations (\"Fos-tagging\"), we show that olfactory fear conditioning activates sparse and distributed ensembles of neurons in mouse piriform cortex. We demonstrate that chemogenetic silencing of these Fos-tagged piriform ensembles selectively interferes with odor fear memory retrieval, but does not compromise basic odor detection and discrimination. Furthermore, chemogenetic reactivation of piriform neurons that were Fos-tagged during olfactory fear conditioning causes a decrease in exploratory behavior, mimicking odor-evoked fear memory recall. Together, our experiments identify odor-specific ensembles of piriform neurons as necessary and sufficient for odor fear memory recall.

neuroscience↗

bioRxiv2018

Robustness of STDP to spike timing jitter

In Hebbian plasticity, neural circuits adjust their synaptic weights depending on patterned firing of action potential on either side of the synapse. Spike-timing-dependent plasticity (STDP) is an experimental implementation of Hebbs postulate that relies on the precise order and the millisecond timing of the paired activities in pre- and postsynaptic neurons. In recent years, STDP has attracted considerable attention in computational and experimental neurosciences. However, canonical STDP is assessed with deterministic (constant) spike timings and time intervals between successive pairings, thus exhibiting a regularity that strongly differs from the biological variability. Hence, the emergence of STDP from noisy neural activity patterns as expected in in vivo-like firing remains unresolved. Here, we used noisy STDP stimulations where the spike timing and/or the interval between successive pairings were jittered. We explored with a combination of experimental neurophysiology and mathematical modeling, the impact of jittering on three distinct forms of STDP at corticostriatal synapses: NMDAR-mediated tLTP, endocannabinoid-mediated tLTD and endocannabinoid-mediated tLTP. As the main result, we found a differential sensitivity to jittered spike timing: NMDAR-tLTP was highly fragile whereas endocannabinoid-plasticity (tLTD and tLTP) appeared more resistant. Moreover, when the frequency or the number of pairings was increased, NMDAR-tLTP became more robust and could be expressed despite strong jittering of the spike timing. Taken together, our results identify endocannabinoid-mediated plasticity as a robust form of STDP while the sensitivity to jitter of NMDAR-tLTP varies with activity frequency. This provides new insights into the mechanisms at play during the different phases of learning and memory and the emergence of Hebbian plasticity in in vivo-like firing.

neuroscience↗