Biology subjects

Caprioli, D.

Publications and source records attributed to Caprioli, D..

4 recordsLinked to original sources

bioRxiv2025

Sex-dimorphic effects of neuromelanin buildup in rodent nigral dopamine neurons: implications for sex-biased vulnerability in Parkinson's disease

Neuromelanin (NM) is a dark pigment accumulating with age in human substantia nigra pars compacta (SNpc) dopamine (DA) neurons, conferring the dark look that inspired nigral areas name. Despite NM has long been associated with Parkinsons disease (PD), as melanized neurons favorably degenerate during disease development, NM functions within SNpc DA neurons are still mostly elusive. Here, by exploiting an NM-producing rat model generated by viral vector-induced expression of human Tyrosinase (hTyr), we inspected NM impact on nigral DA neurons survival and activity, on mitochondrial functionality of SNpc, and behaviors resembling non-motor and motor PD symptoms. Our data reveal sex dimorphism in NM effects on nigrostriatal dopamine circuit, with sex-biased alterations in neuronal firing activity and underlying intrinsic currents, nigral mitochondrial functions, and non-motor PD symptoms (anxiety). In conclusion, this study discloses unrealized NM effects within nigral DA neurons, advancing our comprehension of sex-specific features shaping sex-biased vulnerability to PD.

neuroscience↗

bioRxiv2025

Distinct prelimbic cortex ensembles encode response execution and inhibition

Learning when to initiate or withhold actions is essential for survival and requires integration of past experiences with new information to adapt to changing environments. While stable prelimbic cortex (PL) ensembles have been identified during reward learning, it remains unclear how they adapt when contingencies shift. Does the same ensemble adjust its activity to support behavioral suppression upon reward omission, or is a distinct ensemble recruited for this new learning? We used single-cell calcium imaging to longitudinally track PL neurons in rats across operant food reward Training, Extinction and Reinstatement, trained rat-specific decoders to predict trial-wise behavior, and implemented an in-silico deletion approach to characterize ensemble contributions to behavior. We show that operant training and extinction recruit distinct PL ensembles that encode response execution and inhibition, and that both ensembles are re-engaged and maintain their roles during Reinstatement. These findings highlight ensemble-based encoding of multiple learned associations within a region, with selective ensemble recruitment supporting behavioral flexibility under changing contingencies.

neuroscience↗

bioRxiv2024

Translating human drug use patterns into rat models: exploring spontaneous interindividual differences via refined drug self-administration procedures

Heroin and cocaine users tailor their dosage and frequency of use, as well as their method of administration, to maximize the drugs pleasurable effects and prevent withdrawal symptoms. On the other hand, many preclinical self-administration and choice experiments employ fixed unit doses and mandatory timeouts after doses (known as discrete dimension procedures). These restrictions fail to consider the distinct pharmacokinetic properties of heroin and cocaine, leading to uniform and comparable behaviors (including drug-taking patterns). This uniformity contrasts sharply with the significantly different ways humans use heroin and cocaine, which are characterized by highly individualized drug use behaviors. Here, we introduce a no-timeout procedure that overcomes this limitation (continuous dimension procedure). We analyzed the heroin and cocaine taking- and seeking-patterns and estimated drug-brain levels in the presence or absence of timeout between drug injections. We further assessed how absence of timeout and the availability of drug or social peer (access time to the two rewards) affect drug preference. Removing the timeout had a profound effect on pattern of heroin taking and seeking, promoting the emergence of burst-like drug intake and social withdrawal as revealed by a discrete choice procedure. On the other hand, timeout removal had a lesser impact on cocaine taking and seeking and did not impact social preference. By removing timeout during self-administration and increasing the access time during choice resulted in a self-administration procedure that more closely mimic human heroin intake, offering a platform to identify novel medications.

neuroscience↗

bioRxiv2021

Microglia control glutamatergic synapses in the adult mouse hippocampus

Microglial cells are active players in regulating synaptic development and plasticity in the brain. However, how these cells influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological depletion of microglia, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features accompanied by higher levels of plasticity. In addition, microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. Remarkably, microglial repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in synaptic organization and activity of glutamatergic synapses.

neuroscience↗