arXiv subjects

Alfredo J. Garcia III

Publications and source records attributed to Alfredo J. Garcia III.

2 recordsLinked to original sources

arXiv2026

Dual Mechanisms for Heterogeneous Responses of Inspiratory Neurons to Noradrenergic Modulation

Respiration is an essential involuntary function necessary for survival. This poses a challenge for the control of breathing. The preBötzinger complex (preBötC) is a heterogeneous neuronal network responsible for driving the inspiratory rhythm. While neuromodulators such as norepinephrine (NE) allow it to be both robust and flexible for all living beings to interact with their environment, the basis for how neuromodulation impacts neuron-specific properties remains poorly understood. In this work, we examine how NE influences different preBötC neuronal subtypes by modeling its effects through modulating two key parameters: calcium-activated nonspecific cationic current gating conductance ($g_{\rm CAN}$) and inositol-triphosphate ($\rm IP_3$), guided by experimental studies. Our computational model captures the experimentally observed differential effects of NE on distinct preBötC bursting patterns. We show that this dual mechanism is critical for inducing conditional bursting and identify specific parameter regimes where silent neurons remain inactive in the presence of NE. Furthermore, using methods of dynamical systems theory, we uncover the mechanisms by which NE differentially modulates burst frequency and duration in NaP-dependent and CAN-dependent bursting neurons. These results align well with previously reported experimental findings and provide a deeper understanding of cell-specific neuromodulatory responses within the respiratory network.

q-bio.NC↗

arXiv2017

Different roles for inhibition in the rhythm-generating respiratory network

Unraveling the interplay of excitation and inhibition within rhythm-generating networks remains a fundamental issue in neuroscience. We use a biophysical model to investigate the different roles of local and long-range inhibition in the respiratory network, a key component of which is the pre-Bötzinger complex inspiratory microcircuit. Increasing inhibition within the microcircuit results in a limited number of out-of-phase neurons before rhythmicity and synchrony degenerate. Thus, unstructured local inhibition is destabilizing and cannot support the generation of more than one rhythm. A two-phase rhythm requires restructuring the network into two microcircuits coupled by long-range inhibition in the manner of a half-center. In this context, inhibition leads to greater stability of the two out-of-phase rhythms. We support our computational results with in vitro recordings from mouse pre-Bötzinger complex. Partial excitation block leads to increased rhythmic variability, but this recovers following blockade of inhibition. Our results support the idea that local inhibition in the pre-Bötzinger complex is present to allow for descending control of synchrony or robustness to adverse conditions like hypoxia. We conclude that the balance of inhibition and excitation determines the stability of rhythmogenesis, but with opposite roles within and between areas. These different inhibitory roles may apply to a variety of rhythmic behaviors that emerge in widespread pattern generating circuits of the nervous system.

q-bio.NC↗