Biology subjects

Lucantonio, F.

Publications and source records attributed to Lucantonio, F..

4 recordsLinked to original sources

bioRxiv2025

Ventral striatal astrocytes contribute to reinforcement learning

Astrocytes influence synaptic plasticity and neuronal function through astrocytic calcium dynamics (ACD). However, astrocytes contribution to cognitive operations like reinforcement learning (RL) remains unclear. To examine this, we trained mice on a RL dependent probabilistic decision-making task. We attenuated ACD across distinct striatal regions, and found ACD attenuation specifically in ventral striatum (VS) increased decision noisiness and impaired reward-guided choice performance. This effect was largely due to a reduction in "win-stay" behavior. Using in-vivo calcium imaging, we found that VS ACD correlated with reward prediction errors (RPEs). Furthermore, these trial-by-trial ACD fluctuations predicted trial-by-trial choice variability. In-silico lesions of a biologically constrained circuit model suggest that astrocytes could regulate behavioral variability by sharing RPE signals across populations of striatal neurons. Together, these results suggest that VS astrocytes contribute to cortico-striatal functions to mediate decision noisiness.

neuroscience↗

bioRxiv2023

Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

Ketamines role in providing a rapid and sustained antidepressant response, particularly for patients unresponsive to conventional treatments, is increasingly recognized. A core symptom of depression, anhedonia, or the loss of enjoyment or interest in previously pleasurable activities, is known to be significantly alleviated by ketamine. While several hypotheses have been proposed regarding the mechanisms by which ketamine alleviates anhedonia, the specific circuits and synaptic changes responsible for its sustained therapeutic effects are not yet understood. Here, we show that the nucleus accumbens (NAc), a major hub of the reward circuitry, is essential for ketamines effect in rescuing anhedonia in mice subjected to chronic stress, a critical risk factor in the genesis of depression in humans. Specifically, a single exposure to ketamine rescues stress-induced decreased strength of excitatory synapses on NAc D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs). By using a novel cell-specific pharmacology method, we demonstrate that this cell-type specific neuroadaptation is necessary for the sustained therapeutic effects of ketamine. To test for causal sufficiency, we artificially mimicked ketamine-induced increase in excitatory strength on D1-MSNs and found that this recapitulates the behavioral amelioration induced by ketamine. Finally, to determine the presynaptic origin of the relevant glutamatergic inputs for ketamine-elicited synaptic and behavioral effects, we used a combination of opto- and chemogenetics. We found that ketamine rescues stress-induced reduction in excitatory strength at medial prefrontal cortex and ventral hippocampus inputs to NAc D1-MSNs. Chemogenetically preventing ketamine-evoked plasticity at those unique inputs to the NAc reveals a ketamine-operated input-specific control of hedonic behavior. These results establish that ketamine rescues stress-induced anhedonia via cell-type-specific adaptations as well as information integration in the NAc via discrete excitatory synapses.

neuroscience↗

bioRxiv2021

Neuron-type specificity of dorsal raphe projections to ventral tegmental area

The midbrain dorsal raphe (DR) and ventral tegmental area (VTA) contain two of the brains main ascending neuromodulatory transmitters: serotonin and dopamine. We studied the pathway from DR to VTA using single-cell RNA sequencing, anatomical tracing, and electrophysiology and behavior in mice. Single-cell sequencing confirmed a differential distribution of dopamine cell types between medial and lateral aspects of the VTA. This molecular diversity included differential expression of a subset of glutamatergic and serotonergic receptors. Anatomical data showed that distinct serotonergic and glutamatergic populations of DR neurons project to distinct medial-lateral locations in VTA. Physiological data showed that serotonergic neurons are positioned to excite putative dopaminergic neurons in lateral VTA on short timescales (within trial), and inhibit them on long timescales (on the next trial). Our results reveal precise anatomical specificity of DR projections to VTA, and suggest a functional role for serotonergic modulation of dopaminergic function across multiple timescales.

neuroscience↗

bioRxiv2020

Punishment history biases corticothalamic responses to motivationally-significant stimuli

Making predictions about future rewards or punishments is fundamental to adaptive behavior. These processes are influenced by prior experience. For example, prior exposure to aversive stimuli or stressors changes behavioral responses to negative- and positive-value predictive cues. Here, we demonstrate a role for medial prefrontal cortex (mPFC) neurons projecting to the paraventricular nucleus of the thalamus (PVT; mPFC[->]PVT) in this process. We found that a history of punishments negatively biased behavioral responses to motivationally-relevant stimuli in mice and that this negative bias was associated with hyperactivity in mPFC[->]PVT neurons during exposure to those cues. Furthermore, artificially mimicking this hyperactive response with selective optogenetic excitation of the same pathway recapitulated the punishmentinduced negative behavioral bias. Together, our results highlight how information flow within the mPFC[->]PVT circuit is critical for making predictions about imminent motivationally-relevant outcomes as a function of prior experience.

neuroscience↗