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Rial, D.

Publications and source records attributed to Rial, D..

2 recordsLinked to original sources

Direct and indirect striatal projecting neurons exert strategy-dependent effects on decision-making.

The striatum plays a key role in decision-making, with its effects varying with anatomical location and direct and indirect pathway striatal projecting neuron (d- and i-SPN) populations. Using a mouse gambling task with a reinforcement-learning model, we described of individual decision-making profiles as a combination of three archetypal strategies: Optimizers, Risk-averse, Explorers. Such strategies reflected stable differences in the parameters generating decisions (sensitivity to the reward magnitude, to risk or to punishment) derived from a reinforcement-learning model of animal choice. Chemogenetic manipulation showed that dorsomedial striatum (DMS) neurons substantially impact decision-making, while the nucleus accumbens (NAc) and dorsolateral striatum neurons (DLS) have lesser or no effects, respectively. Specifically, DMS dSPNs decrease risk aversion by increasing the perceived value of risky choices, while DMS iSPNs emphasize large gains, affecting decisions depending on decision-making profiles. Hence, we propose that striatal populations from different subregions influence distinct decision-making parameters, leading to profile-dependent choices.

neuroscience↗

mTOR-RhoA signalling impairments in direct striatal projection neurons induce altered behaviours and striatal physiology in mice

As an integrator of molecular pathways, mTOR has been associated with diseases including neurodevelopmental, psychiatric and neurodegenerative disorders as autism, schizophrenia, and Huntingtons disease. An important brain area involved in all these diseases is the striatum. However, the mechanisms behind how mTOR is involved in striatal physiology and its relative role in distinct neuronal populations in these striatal-related diseases still remain to be clarified. Taking advantage of the D1-mTOR KO mice (males), we combined behavioural, biochemical, electrophysiological and morphological analysis aiming to untangle the role of mTOR in direct pathway striatal projection neurons (dMSNs) and how this would impact on striatal physiology. Our results indicate deep behavioural changes in absence of mTOR in dMSNs such as decreased spontaneous locomotion, impaired social interaction and repetitive behaviour. These were accompanied by a Kv1.1-induced increase in the fast phase of afterhyperpolarization and decreased distal spines density that were mechanistically independent of protein synthesis but dependent of RhoA activity. These results identify mTOR RhoA signaling as an important regulator of striatal functions through an intricate mechanism involving RhoA and culminating in Kv1.1 overfunction, which could be targeted to treat striatal-related mTORopathies.

neuroscience↗