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Baravalle, R.

Publications and source records attributed to Baravalle, R..

4 recordsLinked to original sources

Corticospinal neuron subpopulations with opposing dynamics converge to shape spinal interneuron computations

Corticospinal neuron (CSN) activation plays a crucial role in orchestrating goal-directed actions, but the functional role of reduced CSN output, a feature conserved across species, remains unknown. By combining population imaging, projection mapping, and modelling in mice performing a Go/NoGo lever push task, we reveal that distinct corticospinal neuron subpopulations with opposing dynamics (i.e. increased or decreased activity) are selectively associated with skilled movement execution. Both activity profiles are observed throughout CSN somatodendritic compartments and are spatially organized, with increased activity concentrated in upper layer 5B and decreased activity localized to deeper subregions. Notably, single neuron projection mapping revealed that opposing CSN signals converge onto shared spinal interneurons, while modelling showed that reduced CSN output drives subtractive modulation of spinal interneuron input-output transformations, avoiding output saturation and enabling flexible scaling of output firing rates. These findings redefine corticospinal function by demonstrating that reduced output in a subpopulation of CSNs is critical for shaping spinal cord computations during skilled movement execution.

neuroscience↗

Fast spiking interneurons autonomously generate fast gamma oscillations in the medial entorhinal cortex with excitation strength tuning ING-PING transitions

Gamma oscillations (40-140 Hz) play a fundamental role in neural coordination, facilitating communication and cognitive functions in the medial entorhinal cortex (mEC). While previous studies suggest that pyramidal-interneuron network gamma (PING) and interneuron network gamma (ING) mechanisms contribute to these oscillations, the precise role of inhibitory circuits remains unclear. Using optogenetic stimulation and whole-cell electrophysiology in acute mouse brain slices, we examined synaptic input and spike timing in neurons across layer II/III mEC. We found that fast-spiking interneurons exhibited robust gamma-frequency firing, while excitatory neurons engaged in gamma cycle skipping. Stellate and pyramidal cells received minimal recurrent excitation, whereas fast-spiking interneurons received strong excitatory input. Both excitatory neurons and fast-spiking interneurons received gamma frequency inhibition, emphasizing the role of recurrent inhibition in gamma rhythm generation. Notably, gamma activity was reduced, but persisted after AMPA/kainate receptor blockade, indicating that interneurons can sustain gamma oscillations independently through an ING mechanism. Selective activation of PV+ interneurons confirmed their ability to sustain fast gamma inhibition autonomously. To further assess the interplay of excitation and inhibition, we developed computational network models constrained by our experimental data. Simulations revealed that weak excitatory input to interneurons supports fast ING-dominated rhythms ([~]100-140 Hz), while strengthening excitatory drive induces a transition to slower PING-dominated oscillations (60-100 Hz). These findings highlight the dominant role of inhibitory circuits in sustaining gamma rhythms, demonstrate how excitation strength tunes the oscillatory regime, and refine models of entorhinal gamma oscillations critical for spatial memory processing. Significance StatementGamma oscillations in the medial entorhinal cortex (mEC) are essential for spatial navigation and memory, yet the mechanisms underlying their generation remain unresolved. Combining optogenetics, whole-cell electrophysiology, and computational modeling, we show that fast-spiking interneurons can autonomously sustain gamma rhythms via interneuron network gamma (ING). Blocking excitatory input reduced, but did not abolish gamma-frequency inhibition, and selective activation of PV+ interneurons confirmed their capacity to generate fast gamma independently. Modeling revealed that excitatory strength tunes the oscillatory regime, with weak excitation favoring fast ING and stronger excitation inducing slower pyramidal-interneuron network gamma (PING). These findings refine entorhinal gamma models and suggest a hybrid mechanism for switching between faster and slower gamma critical for spatial computation.

neuroscience↗

Synchrony in Networks of Type 2 Interneurons is More Robust to Noise with Hyperpolarizing Inhibition Compared to Shunting Inhibition in Both the Stochastic Population Oscillator and the Coupled Oscillator Regimes

Synchronization in the gamma band (30-80 Hz) is mediated by PV+ inhibitory interneurons, and evidence is accumulating for the essential role of gamma oscillations in cognition. Oscillations can arise in inhibitory networks via synaptic interactions between individual oscillatory neurons (mean-driven) or via strong recurrent inhibition that destabilizes the stationary background firing rate in the fluctuation-driven balanced state, causing an oscillation in the population firing rate. Previous theoretical work focused on model neurons with Hodgkins type 1 excitability (integrators) connected by current-based synapses. Here we show that networks comprised of simple type 2 oscillators (resonators) exhibit a supercritical Hopf bifurcation between synchrony and asynchrony and a gradual transition via cycle skipping from coupled oscillators to stochastic population oscillator, as previously shown for type 1. We extended our analysis to homogeneous networks with conductance rather than current based synapses and found that networks with hyperpolarizing inhibitory synapses were more robust to noise than those with shunting synapses, both in the coupled oscillator and stochastic population oscillator regime. Assuming that reversal potentials are uniformly distributed between shunting and hyperpolarized values, as observed in one experimental study, converting synapses to purely hyperpolarizing favored synchrony in all cases, whereas conversion to purely shunting synapses made synchrony less robust except at very high conductance strengths. In mature neurons the synaptic reversal potential is controlled by chloride cotransporters that control the intracellular concentrations of chloride and bicarbonate ions, suggesting these transporters as a potential therapeutic target to enhance gamma synchrony and cognition. Significance StatementBrain rhythms in the gamma frequency band (30-80 Hz) depend on the activity of inhibitory interneurons and evidence for a causal role for gamma oscillations in cognitive functions is accumulating. Here we extend previous studies on synchronization mechanisms to interneurons that have an abrupt threshold frequency below which they cannot sustain firing. In addition to current based synapses, we examined inhibitory networks with conductance based synapses. We found that if the reversal potential for inhibition was below the average membrane potential (hyperpolarizing), synchrony was more robust to noise than if the reversal potential was very close to the average potential (shunting). These results have implications for therapies to ameliorate cognitive deficits.

neuroscience↗

Anomalous brain energy in old age by wavelet analysis of ERP during a Stroop task

By event-related potentials (ERP) during a counting Stroop task it was shown that the elderly with excess in theta activity in their electroencephalogram (EEG) are at risk of cognitive decline and have a higher neuronal activity during stimulus categorization than the elderly with a normal EEG. It was suggested that this increased neuronal activity could have a compensatory function. However, the quantification of energy associated with the enhanced neuronal activity was not investigated in this group. By wavelet analysis, we measured total and relative energy in ERP during the execution of a counting Stroop task in two groups of elderly: one with excess in theta activity (Theta-EEG, n = 23) and the other with normal EEG (Normal-EEG, n = 23). In delta, theta, and alpha bands, the Theta-EEG group used a higher amount of total energy as compared to the Normal-EEG group for both types of stimuli, interference and no interference. In theta and alpha bands, the total energy was higher in the Theta-EEG group, specifically in the window of 258-516 ms, coinciding with stimulus categorization. Given that no major behavioral differences were observed between EEG groups, we suggest that a higher energy in delta, theta, and alpha bands is one of the neurobiological mechanisms that allows the Theta-EEG group to cope with the cognitive demands of the task. However, this increased energy might not be an effective mechanism in the long term as it could promote a metabolic and cellular dysregulation that would trigger the transition to cognitive impairment. SIGNIFICANCE STATEMENTBy using wavelet transform analysis we report that the elderly with excess in theta activity show a higher energy in delta, theta, and alpha bands during the categorization of stimuli in a counting Stroop task. Our findings imply that this increase neuronal activity might be related to a dysregulated energy metabolism in the elderly with theta excess that could explain the progress to cognitive impairment in this group. The analysis of energy by wavelet transform in data obtained by ERP complements other techniques that evaluate the risk of cognitive impairment.

neuroscience↗