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Mansourian, K.

Publications and source records attributed to Mansourian, K..

2 recordsLinked to original sources

Mirror manifolds: partially overlapping neural subspaces for speaking and listening

We utilize internal representations of meaning for two purposes: to understand the words we hear and to generate our own speech. This dual requirement necessitates abstract, modality-agnostic representations. Building on work identifying it as a hub for relational mapping, we hypothesized that the hippocampus supports abstract, cross-person representations, and uses shared semantic geometries to do so. We tested this hypothesis by examining hippocampal activity in a remarkable single-neuron dataset derived from conversational speech. Neurons robustly encoded meanings of both spoken and heard words, and used common geometric embeddings for both, leading to abstract meaning performance. Speaker identity was aligned with meaning via partial subspace alignment, which affords speaker-meaning binding by partitioning meaning by speaker while maintaining cross-speaker generalization. Degrees of subspace rotation varied on a single word level and depended systematically on semantic category. Together, these findings indicate how geometric principles allow for abstract cross-personal meanings while preserving binding to speaker identity.

neuroscience↗

A diencephalic circuit for opioid analgesia but not positive reinforcement

Mu opioid receptor (MOR) agonists are potent analgesics, but also cause sedation, respiratory depression, and addiction risk. The epithalamic lateral habenula (LHb) signals aversive states including pain and we found it is a potent site for MOR-agonist analgesia. Importantly, LHb MOR activation is not reinforcing in the absence of noxious input. The LHb receives excitatory inputs from multiple sites including the ventral tegmental area, lateral hypothalamus, entopeduncular nucleus, and the lateral preoptic area of the hypothalamus (LPO). Here we report that LHb-projecting glutamatergic LPO neurons are excited by noxious stimulation and are preferentially inhibited by MOR selective agonists. Critically, optogenetic stimulation of LHb-projecting LPO neurons produces an aversive state that is relieved by LHb MOR activation, and optogenetic inhibition of LHb-projecting LPO neurons relieves the aversiveness of ongoing pain. Therefore, targeting this MOR sensitive forebrain circuit can relieve pain yet lower the risk of misuse by pain free individuals.

neuroscience↗