Biology subjects

Torrado Pacheco, A.

Publications and source records attributed to Torrado Pacheco, A..

4 recordsLinked to original sources

bioRxiv2023

Acute psilocybin enhances cognitive flexibility in rats

Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2A receptor antagonist ketanserin blocked psilocybins effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybins pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.

neuroscience↗

bioRxiv2019

Sleep promotes downward firing rate homeostasis

Homeostatic plasticity is hypothesized to regulate neuronal activity around a stable set point to compensate for learning-related plasticity. This regulation is predicted to be bidirectional but only upward firing rate homeostasis (FRH) has been demonstrated in vivo. We combined chronic electrophysiology in freely behaving animals with a protocol that induces robust plasticity in primary visual cortex (V1) to induce downward FRH and show that neurons bidirectionally regulate firing rates around an individual set point. Downward FRH did not require N-methyl-D-aspartate receptor (NMDAR) signaling and was associated with homeostatic scaling down of synaptic strengths. Like upward FRH, downward FRH was gated by vigilance state, but in the opposite direction: it occurred during sleep and not during wake. In contrast, FR changes associated with Hebbian plasticity happened independently of sleep and wake. Thus, we find that sleeps impact on neuronal plasticity depends on the particular forms of plasticity that are engaged.

neuroscience↗

bioRxiv2019

Rapid and Active Stabilization of Visual Cortical Firing Rates Across Light-Dark Transitions

The dynamics of neuronal firing during natural vision are poorly understood. Surprisingly, mean firing rates of neurons in primary visual cortex (V1) of freely behaving rodents are similar during prolonged periods of light and darkness, but it is unknown whether this reflects a slow adaptation to changes in natural visual input, or insensitivity to rapid changes in visual drive. Here we use chronic electrophysiology in freely behaving rats of either sex to follow individual V1 neurons across many dark-light (D-L) and light-dark (L-D) transitions. We show that, even on rapid timescales (1s to 10 min), neuronal activity was only weakly modulated by transitions that coincided with the expected 12h/12h light-dark cycle. In contrast, a larger subset of V1 neurons consistently responded to unexpected L-D and D-L transitions, and disruption of the regular L-D cycle with 60 hours of complete darkness induced a robust increase in V1 firing upon re-introduction of visual input. Thus, V1 neurons fire at similar rates in the presence or absence of natural stimuli, and significant changes in activity arise only transiently in response to unexpected changes in the visual environment. Further, although mean rates were similar in L and D, pairwise correlations were significantly stronger during natural vision, suggesting that information about natural scenes in V1 is more readily extractable from correlations than from individual firing rates. Together, our findings show that V1 firing rates are rapidly and actively stabilized during expected changes in visual input, and are remarkably stable at both short and long timescales.

neuroscience↗

bioRxiv2018

Autism-associated Shank3 is essential for homeostatic plasticity and neuronal circuit stability

Mutations in Shank3 are strongly associated with autism spectrum disorders and circuit disfunction, but a unified view of how Shank3 loss disrupts circuit function and excitability is lacking. Stabilizing, homeostatic forms of synaptic and intrinsic plasticity are critical for preventing circuit hyper- or hypo-excitability, leading us to ask whether Shank3 loss perturbs circuits by disrupting homeostatic plasticity. We show that Shank3 loss abolishes synaptic and intrinsic homeostatic plasticity, which can be rescued by lithium(Li), a drug with therapeutic potential in human Shankopathies. Further, Shank3 loss in vivo severely compromises the ability of visual cortical circuits to recover from perturbations to sensory drive. Our findings suggest that the loss of homeostatic compensation is a critical endophenotype that can explain a range of circuit disfunctions in Shankopathies.

neuroscience↗