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Fuenzalida, M.

Publications and source records attributed to Fuenzalida, M..

3 recordsLinked to original sources

Optogenetic disruption of neural dynamics in the prefrontal cortex impaired spatial learning

1.Cortical neural activity is highly dynamical at several temporal scales, property that has been postulated to be critical for the emergence of specific patterns supporting cognitive operations. During spatial learning, task-associated activity patterns gradually develop in the medial prefrontal cortex (mPFC) as the subject acquires experience. If neural activity dynamics is required in the mPFC for spatial learning is still unclear. Here we show that optogenetic entrainment of neural activity the mPFC disrupted local oscillatory and single-neuron dynamics. When applied during spatial training, optogenetic entrainment impaired behavioral performance and navigation strategy progression, a hallmark of spatial learning supported by the mPFC. Also, optogenetic entrainment blocked the emergence of learning-related activity patterns such as cross-frequency coupling and firing patterns signaling efficient goal approaching. Importantly, during memory retrieval, training-stimulated mice showed impaired performance in the absence of optogenetic stimulation. This evidence show that neural activity dynamics in the mPFC is crucial for spatial learning. SignificanceCortical neural activity is highly fluctuating at several temporal scales, which has been postulated to be critical for cognitive functions. The medial prefrontal cortex (mPFC) is involved in the learning-related optimization of behavioral responses; however, it is unknown whether the dynamics of neural activity in the mPFC is required for learning. Here we found that optogenetic disruption of ongoing neural activity dynamics in the mPFC during training in a spatial memory acquisition task impaired spatial learning and hindered the emergence of learning-related activity patterns. These findings provide insight into the role of prefrontal activity dynamics in cognitive functions.

neuroscience↗

Maternal Immune Activation Alters Temporal Precision of Spike Generation of CA1 Pyramidal Neurons by Unbalancing GABAergic Inhibition in the Offspring

Maternal immune activation (MIA) represents a risk factor for neuropsychiatric disorders associated with neurodevelopmental alterations. A growing body of evidence from rodents and non-human primates shows that MIA induced by viral or bacterial infections results in several neurobiological alterations in the offspring. These changes may play an important role in the pathophysiology of psychiatric disorders like schizophrenia and autism spectrum disorders, whose clinical features include impairments in cognitive processing and social performance. Such alterations are causally associated with the maternal inflammatory response to infection rather than with the infection itself. Previously, we reported that CA1 pyramidal neurons of mice exposed to MIA exhibit increased excitability accompanied by a reduction in dendritic complexity. However, potential alterations in cellular and synaptic rules that shape the neuronal computational properties of the offspring remain to be determined. In this study, using mice as subjects, we identified a series of cellular and synaptic alterations endured by CA1 pyramidal neurons of the dorsal hippocampus in a lipopolysaccharide-induced MIA model. Our data provide evidence that MIA reshapes the excitation-inhibition balance by decreasing the perisomatic GABAergic inhibition impinging on CA1 pyramidal neurons. These alterations yield a dysregulated amplification of the temporal and spatial synaptic integration. In addition, MIA-exposed offspring displayed social and anxiety-like abnormalities. Collectively, these findings contribute to the understanding of the cellular and synaptic alterations underlying the behavioral symptoms present in neurodevelopmental disorders associated with MIA. HighlightsO_LILPS injection during pregnancy (MIA) increases cytokine production and decreases litter size. C_LIO_LIMIA increases the temporal summation of EPSPs in hippocampal neurons. C_LIO_LIMIA alters spatial summation and increases the probability of action potential discharge. C_LIO_LIMIA alters the inhibitory/excitatory balance of CA1 pyramidal cells. C_LIO_LIMIA alters the expression of GAD-positive interneurons. C_LIO_LIMIA alters the performance of several behavioral tests in offspring. C_LI

neuroscience↗

Long-term Pannexin 1 ablation promotes structural and functional modifications in hippocampal neurons through the regulation of actin cytoskeleton and Rho GTPases activity.

Enhanced activity and overexpression of Pannexin 1 (PANX1) channels contribute to neuronal pathologies, such as epilepsy and Alzheimers disease (AD). In the hippocampus, the PANX1 channels ablation alters glutamatergic neurotransmission, synaptic plasticity, and memory flexibility. Nevertheless, PANX1-knockout (KO) mice still preserve the ability to learn, suggesting that compensatory mechanisms work to stabilize neuronal activity. Here, we show that the absence of PANX1 in the adult brain promotes a series of structural and functional modifications in KO hippocampal synapses, preserving spontaneous activity. Adult CA1 neurons of KO mice exhibit enhanced excitability, complex dendritic branching, spine maturation, and multiple synaptic contacts compared to the WT condition. These modifications seem to rely on the actin-cytoskeleton dynamics as an increase in actin polymerization and an imbalance between Rac1 and RhoA GTPase activity is observed in the absence of PANX1. Our findings highlight a novel interaction between PANX1, actin, and small Rho GTPases that appear to be relevant for synapse maintenance as a long-term compensatory mechanism for PANX1 deficiency.

neuroscience↗