Biology subjects

Sehgal, M.

Publications and source records attributed to Sehgal, M..

4 recordsLinked to original sources

bioRxiv2021

Miniscope-LFOV: A large field of view, single cell resolution, miniature microscope for wired and wire-free imaging of neural dynamics in freely behaving animals

Imaging large-population, single-cell fluorescent dynamics in freely behaving animals larger than mice remains a key endeavor of neuroscience. We present a large field of view open-source miniature microscope (MiniLFOV) designed for large-scale (3.6 x 2.7 mm), single cell resolution neural imaging in freely behaving rats. It has an electrically adjustable working distance of up to 3.5 mm{+/-}100 m, incorporates an absolute head-orientation sensor, and weighs only 13.9 grams. The MiniLFOV is capable of both deep brain and cortical imaging and has been validated in freely behaving rats by simultaneously imaging >1000 GCaMP7s expressing neurons in the hippocampal CA1 layer and in head-fixed mice by simultaneously imaging ~2000 neurons in the dorsal cortex through a cranial window. The MiniLFOV also supports optional wire-free operation using a novel, wire-free data acquisition expansion board. We expect this new open-source implementation of the UCLA Miniscope platform will enable researchers to address novel hypotheses concerning brain function in freely behaving animals.

neuroscience↗

bioRxiv2021

Co-allocation to overlapping dendritic branches in the retrosplenial cortex integrates contextual memories across time

Events occurring close in time are often linked in memory, providing an episodic timeline and a framework for those memories. Recent studies suggest that memories acquired close in time are encoded by overlapping neuronal ensembles, but the role of dendritic plasticity mechanisms in linking memories is unknown. Using activity-dependent labeling and manipulation approaches, longitudinal one- and two-photon imaging of somatic and dendritic compartments, and computational modeling, we show that memory linking is not only dependent on ensemble overlap in the retrosplenial cortex, but also on branch-specific dendritic allocation mechanisms. The same dendritic segments are preferentially activated by two linked memories, and spine clusters added after each of the two linked memories are allocated to the same dendritic segments. Our results demonstrate a causal mechanistic role for dendritic plasticity in memory integration and reveal a novel set of rules that govern how linked and independent memories are allocated to dendritic compartments.

neuroscience↗

bioRxiv2021

A retrograde mechanism coordinates memory allocation across brain regions

Memories engage ensembles of neurons across different brain regions within a memory system. However, it is unclear whether the allocation of a memory to these ensembles is coordinated across brain regions. To address this question, we used CREB expression to bias memory allocation in one brain region, and rabies retrograde tracing to test memory allocation in connected presynaptic neurons in the other brain regions. We find that biasing allocation of CTA memory in the basolateral amygdala (BLA) also biases memory allocation in presynaptic neurons of the insular cortex (IC). By manipulating the allocation of CTA memory to specific neurons in both BLA and IC, we found that we increased their connectivity and enhanced CTA memory performance. These results - which are corroborated by mathematical simulations, and by studies with auditory fear conditioning - demonstrate that a retrograde mechanism coordinates the allocation of memories across different brain regions.

neuroscience↗

bioRxiv2021

Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape from innate and conditioned threats. The hypothalamic dorsal premammillary nucleus (PMd) may control escape, as it is activated by escape-inducing threats and projects to the region most implicated in flight, the dorsolateral periaqueductal gray (dlPAG). We show that in mice cholecystokinin (cck)-expressing PMd cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Lastly, human fMRI data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd as a central node of the escape network.

neuroscience↗