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Dhanasobhon, D.

Publications and source records attributed to Dhanasobhon, D..

3 recordsLinked to original sources

A dendritic substrate for temporal diversity of cortical inhibition

In the mammalian neocortex, GABAergic interneurons (INs) inhibit cortical networks in profoundly different ways. The extent to which this depends on how different INs process excitatory signals along their dendrites is poorly understood. Here, we reveal that the functional specialization of two major populations of cortical INs is determined by the unique association of different dendritic integration modes with distinct synaptic organization motifs. We found that somatostatin (SST)-INs exhibit NMDAR-dependent dendritic integration and uniform synapse density along the dendritic tree. In contrast, dendrites of parvalbumin (PV)-INs exhibit passive synaptic integration coupled with proximally enriched synaptic distributions. Theoretical analysis shows that these two dendritic configurations result in different strategies to optimize synaptic efficacy in thin dendritic structures. Yet, the two configurations lead to distinct temporal engagement of each IN during network activity. We confirmed these predictions with in vivo recordings of IN activity in the visual cortex of awake mice, revealing a rapid and linear recruitment of PV-INs as opposed to a long-lasting integrative activation of SST-INs. Our work reveals the existence of distinct dendritic strategies that confer distinct temporal representations for the two major classes of neocortical INs and thus dynamics of inhibition.

neuroscience↗

Feedforward circuits enable modality-specific control of cortical inhibition during behavioral state transitions.

Local inhibitory neurons (INs), specifically those involved in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-positive INs, are essential for regulating cortical function during behavior. However, it is unclear the mechanisms by which these INs are recruited during active states and whether their activity is consistent across different sensory cortices. We now reveal that in mice, locomotor activity strongly recruits SST-INs in primary somatosensory (S1) but not visual (V1) cortex. This diverse engagement of SST-INs could not be explained by differences in VIP-IN function but was absent in the presence of visual sensory drive suggesting involvement of feedforward sensory pathways. In agreement, inactivating the somatosensory thalamus, but not decreasing VIP-INs activity, significantly reduces the recruitment of SST-INs in S1 by locomotion. Finally, model simulations suggest differences in SST-INs activity can be explained by varying ratios of VIP-driven inhibition and thalamus-driven cortical excitation. Our work suggests that by integrating feedforward activity with neuromodulation, SST-INs play a central role in adapting sensory processing to behavioral states.

neuroscience↗

Enhanced analgesic cholinergic tone after neuropathy

At the spinal cord level, a tone of endogenous acetylcholine (ACh) modulates nociceptive sensory processing. Increasing the level of spinal ACh induces analgesia in naive animals or in situation of acute pain in the clinics, but whether this is still the case in situations or models of chronic pain is controversial. Here, we demonstrate the persistence, and even increased impact of the analgesic cholinergic tone acting through nicotinic receptors in neuropathic mice. The neuropathy does not affect the number and properties of dorsal horn cholinergic neurons, proposed to be the source of spinal ACh. Subthreshold doses of acetylcholinesterase (AChE) inhibitors in sham animals become anti-allodynic in cuff mice suggesting that the alterations occur in the cholino-receptive neurons. Thus endogenous cholinergic signaling can be manipulated with low doses of drugs to relieve mechanical allodynia in animal neuropathy models. This opens new avenues with potentially fewer side effects for neuropathic pain treatment.

neuroscience↗