Biology subjects

Bariselli, S.

Publications and source records attributed to Bariselli, S..

9 recordsLinked to original sources

bioRxiv2023

Motor cortex somatostatin interneurons adaptively shape the structure of motor sequences

The brain can flexibly reorganize the structure of action sequence, or motor programs, to efficiently reach positive outcomes. These behavioral adaptations are primarily driven by reinforcement learning, leading to structural and kinematic modifications of consolidated motor programs. While the motor cortex is recognized as a crucial neural substrate for adaptive motor control and skill learning, the mechanisms by which cortical microcircuits actively fine-tune the timing and structure of action sequences, enabling organisms to adaptively maintain motor efficiency across varying task demands, remain unclear. Here, we found that the calcium activity of somatostatin (SST) interneurons (INs) in the primary motor cortex (M1) exhibits highly action-locked and synchronized calcium responses during the acquisition of a single lever-press task in freely moving mice. This neural representation contrasts with the sequential activation of pyramidal (PYR) neurons during the same task. After extended training with a consistent schedule and subsequent motor consolidation, M1 SST IN activity was no longer related to action execution. However, when the training schedule was progressively updated, leading mice to adapt their motor programs for more time-constrained, rapid action sequences, the action-related SST IN activity redistributed and did not decrease. Notably, this redistributed calcium activity of M1 SST INs correlated with structural modulation of ongoing action sequences. We identified two distinct neural activity patterns among non-overlapping SST IN populations: one encoding the initiation of action sequences and the other encoding trial-by-trial structural changes during the execution of complex action sequences. Moreover, inhibition of SST INs disrupted temporal structure of action sequences and decreased the efficiency of motor program execution. These findings highlight the unexpected role of M1 SST interneurons in actively refining motor programs into more efficient and task-specific structures. HIGHLIGHTSO_LIActivation of somatostatin (SST) interneurons in the primary motor cortex (M1) correlates with learning new motor actions and execution of complex motor programs. C_LIO_LIDistinct activity patterns of M1 SST interneurons actively encode the initiation and temporal structure of complex action sequences on a trial-by-trial basis C_LIO_LIInhibition of SST interneuron activity leads to inefficient execution of complex motor programs, with effects dependent on task specificity. C_LI

neuroscience↗

bioRxiv2023

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

While cortico-striatal circuit deficits contribute to Alcohol Use Disorder, the impact of alcohol on synaptic function in the basal ganglia output, the substantia nigra pars reticulata (SNr), remains unclear. Here, we found that the inputs from the dorsomedial (DMS) and dorsolateral striatum (DLS) differ in their presynaptic properties and target molecularly distinct subpopulations of SNr neurons. We also discovered that indirect pathway subthalamic (STN) inputs to the medial and lateral SNr have different presynaptic properties and that STN inputs are stronger in the lateral SNr. Chronic alcohol exposure (CIE) potentiated DLS inputs but did not affect the strength and presynaptic release properties of DMS and subthalamic inputs to SNr neurons. Chemogenetic inhibition of DLS direct pathway projection neurons impaired action performance in an operant conditioning task in CIE mice but not control mice. Overall, our work identifies a synaptic mechanism whereby chronic alcohol induces a gain of function for action control in direct pathway neurons in the dorsolateral striatum. TeaserChronic alcohol selectively potentiates DLS synaptic inputs to the SNr, enhancing their role in action control.

neuroscience↗

bioRxiv2022

Neural correlates for neonicotinoid-induced impairment of olfactory long-term memory

Reports of olfactory learning and memory deficits in honey bees exposed to neonicotinoid pesticides have been accumulating over the past decades. As agonists of the nicotinic receptors to acetylcholine, neonicotinoids target most of the projection neurons conveying olfactory information to the memory brain centres, the mushroom bodies (MBs). However, the neural mechanisms by which neonicotinoids interfere with memory formation are poorly understood. Here, we investigated the consequences of chronic exposure to the neonicotinoid imidacloprid on the number of projection neuron terminal boutons and on their plasticity in the context of long-term memory formation. Using super-resolution STED microscopy, we also measured the density of synapsin-positive units (SPUs) within boutons, as synapsin is known to be enriched in new boutons following neuronal activation. We show that imidacloprid suppresses the synaptic pruning of projection neurons naturally occurring with age and experience. The resulting excessive number of boutons in the MBs of treated bees was associated with long-term memory deficits. The subset of treated bees that showed successful memory formation had a similar number of boutons as untreated bees, suggesting that synaptic pruning might have been involved in the memorization process. As the SPU density was not affected by the imidacloprid treatment, the high bouton number in the lip of treated bees was not due to synaptogenesis. Altogether, our experiments show that, by altering synaptic pruning, imidacloprid interferes with long-term memory formation.

neuroscience↗

bioRxiv2022

Gestational Ethanol Exposure Induces Sex-specific Striatal Acetylcholine and Dopamine Deficits

Fetal alcohol exposure has deleterious consequences on the cognitive abilities and motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of gestational ethanol exposure (GEE). Deficits in striatal cholinergic and dopamine function impair action learning and execution, yet the effects of GEE on striatal acetylcholine and dopamine release remain unexplored. Here, we report that ethanol (EtOH) exposure during the first ten postnatal days (GEEP0-P10), which mimics EtOH consumption during the last gestational trimester in humans, induces enduring sex-specific anatomical and motor learning deficits in female mice. These behavioral impairments were accompanied by increased evoked-dopamine levels in the dorsolateral striatum (DLS) of GEEP0-P10 female, but not male, mice. Further experiments revealed impaired striatal {beta}2-containing nicotinic acetylcholine receptor (nAChRs)-modulation of electrically evoked dopamine release. Using a genetically encoded acetylcholine sensor (GACh3.0), we found a reduced decay of acetylcholine transients in DLS of GEEP0-P10 females in the presence of an acetylcholinesterase inhibitor galantamine. Finally, we showed that this effect is associated with decreased excitability of striatal cholinergic interneurons (CINs), pointing to activity-dependent defects in acetylcholine release. Altogether, these data shed a new light on striatal deficits that might underlie cognitive and motor learning symptoms of patients affected by FASD.

neuroscience↗

bioRxiv2021

Inhibition of TRPV4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism

Autism spectrum disorder is a neurodevelopmental disease characterized by social deficits and repetitive behaviors. The high heterogeneity of the disease may be explained by gene and environmental interactions and potential risk factors include immune dysfunctions and immune-mediated co-morbidities. Mutations in the SHANK3 gene have been recognized as a genetic risk factor for ASD. While heterozygous SHANK3 mutations are usually the types of mutations associated with idiopathic autism in patients, heterozygous deletion of Shank3 gene in mice does not commonly induce ASD-related behavioural deficit. Here, we used in-vivo and ex-vivo approaches to demonstrate that region-specific neonatal downregulation of Shank3 in the NAc promotes D1R-MSN hyperexcitability and upregulates Trpv4 to impair social behaviour. Interestingly, genetically vulnerable Shank3+/- mice, when challenged with Lipopolysaccharide to induce inflammatory response, showed similar circuit and behavioural alterations that were rescued by acute Trpv4 inhibition. Altogether our data demonstrate shared molecular and circuit mechanisms between ASD-relevant genetic alterations and environmental insults, which ultimately lead to sociability dysfunctions.

neuroscience↗

bioRxiv2019

Orbitofrontal-striatal potentiation underlies stimulant induced hyperactivity

Stimulants are one of the most widely prescribed classes of pharmaceuticals, but it is unclear which brain pathways underlie their therapeutic and adverse actions. Here, with real-time monitoring of circuit plasticity, we demonstrate that psychostimulants strengthen orbitofrontal (OFC) to dorsomedial striatum (DMS) pathway synapses, and increase striatal output in awake mice. In vivo high-frequency stimulation of OFC-DMS pathway blocked stimulant-induced potentiation and the expression of locomotor sensitization, thereby directly linking OFC-DMS plasticity to hyperactivity.

neuroscience↗

bioRxiv2019

Superior Colliculus to VTA pathway controls orienting behavior during conspecific interaction.

Social behaviours characterize cooperative, mutualistic aggressive or parental interactions that occurs among conspecifics. Although several neuronal substrates of social behaviour have been identified, whether defined circuits are dedicated to specific aspect of conspecific interaction is still an open question. Ventral Tegmental Area (VTA) contributes to the rewarding properties of conspecific interaction. However, how information related to conspecifics are conveyed to the VTA is still largely unknown. In this study, we identified a population of Superior Colliculus (SC) neurons projecting to the VTA which increase their activity before conspecific interaction and control orienting response towards unfamiliar conspecifics. Finally, we show that SC inputs target a subpopulation of Dopamine (DA) neurons within the VTA that in turn project to dorsolateral striatum (DLS). Our work supports the hypothesis that specialized sub-circuits are dedicated to process different aspect of social interaction.

neuroscience↗

bioRxiv2018

SHANK3 downregulation in the VTA accelerates the extinction of contextual associations induced by non-familiar conspecific interaction

Conditioned place preference (CPP) paradigms, traditionally adopted to study the reinforcing properties of drugs of abuse, have been developed to investigate the neurobiological mechanisms underlying the reinforcing properties of social stimuli. These protocols are largely based on single-housing before and/or during the social stimulus-contextual cues acquisition phase. Here, based on previously established social interaction-induced CPP paradigms, we characterize a place preference task relying on the reinforcing properties of free interaction with a non-familiar (novel) conspecific. The formation of contextual associations induced by the interaction with a novel social stimulus does not require single-housing, necessitates dopamine (DA) receptor 2/3 (D2/3R) activation and undergoes extinction. Interestingly, while extinction of CPP responses is reduced by single-housing, it is accelerated by the downregulation of the autism spectrum disorder (ASD)-related protein SHANK3 in the ventral tegmental area (VTA). Thus, inspired by the literature on drug of abuse-induced contextual learning, we propose that acquisition and extinction of CPP might be used as behavioral assays to assess social-induced contextual association and \"social-seeking\" dysfunctions in animal models of psychiatric disorders.

neuroscience↗

bioRxiv2018

Neuronal signature of social novelty exploration in the VTA: implication for Autism Spectrum Disorder

Novel stimuli attract our attention, promote exploratory behavior, and facilitate learning. Atypical habituation and aberrant novelty exploration have been related with the severity of Autism Spectrum Disorders (ASD) but the underlying neuronal circuits are unknown. Here, we report that dopamine (DA) neurons of the ventral tegmental area (VTA) promote the behavioral responses to novel social stimuli, support preference for social novelty, and mediate the reinforcing properties of novel social interaction. Social novelty exploration is associated with the insertion of calcium-permeable GluA2-lacking AMPA-type glutamate receptors at excitatory synapses on VTA DA neurons. These novelty-dependent synaptic adaptations only persist upon repeated exposure to social stimuli and sustain social interaction. Global or DA neuron-specific inactivation of the ASD risk gene Neuroligin3 alters both social novelty exploration and the reinforcing properties of social stimuli. These behavioral deficits are accompanied by an aberrant expression of non-canonical GluA2-lacking AMPA-receptors at excitatory synapses on VTA DA neurons and an occlusion of novelty-induced synaptic plasticity. Altogether, these findings causally link impaired novelty exploration in an ASD mouse model to VTA DA circuit dysfunction.

neuroscience↗