Search bioRxiv⌕ Search

Biology subjects

Gutkin, B.

Publications and source records attributed to Gutkin, B..

20 records · Page 2Linked to original sources

Development of inhibitory synaptic delay drives maturation of thalamocortical network dynamics

Nervous system maturation occurs on multiple levels, synaptic, circuit, and network, at divergent time scales. For example, many synaptic properties mature gradually, while emergent network dynamics, as data show, change abruptly. Here, we combine experimental and theoretical approaches to investigate a sudden transition in spontaneous thalamocortical activity necessary for the development of vision. Inspired by in vivo measurements of time-scales and amplitudes of synaptic currents, we extend the Wilson and Cowan model to take into account the relative onset timing and amplitudes of inhibitory and excitatory neural population responses. We study the dynamics of this system and identify the bifurcations as the onset timescales of excitation and inhibition are varied. We focus on the specific typical developmental changes in synaptic timescales consistent with the experimental observations. These findings argue that the inhibitory timing is a critical determinant of thalamocortical activity maturation; a gradual decay of the ratio of inhibitory to excitatory onset time below one drives the system through a bifurcation that leads to a sudden switch of the network spontaneous activity from high-amplitude oscillations to a non-oscillatory active state. This switch also drives a marked change to a linear network response to transient stimuli, agreeing to the in vivo observations. The switch observed in the model is representative of the sudden transition in the sensory cortical activity seen early in development.

neuroscience↗

Circuit-level Mechanisms of EtOH-dependent dopamine release.

Alcoholism is the third leading cause of preventable mortality in the world. In the last decades a large body of experimental data has paved the way to a clearer knowledge of the specific molecular targets through which ethanol (EtOH) acts on brain circuits. Yet how these multiple mechanisms play together to result in a dysregulated dopamine (DA) release under alcohol influence remains unclear. In this manuscript, we delineate potential circuit-level mechanisms responsible for EtOH-dependent increase and dysregulation of DA release from the ventral tegmental area (VTA) into nucleus accumbens (Nac). For this purpose, we build a circuit model of the VTA composed of DA and GABAergic neurons, that integrate external Glutamatergic (Glu) inputs to result in DA release. In particular, we reproduced a non-monotonic dose dependence of DA neurons firing activity on EtOH: an increase in firing at small to intermediate doses and a drop below baseline (alcohol-free) levels at high EtOH concentrations. Our simulations predict that a certain level of synchrony is necessary for the firing rate increase produced by EtOH. Moreover, EtOHs effect on the DA neurons firing rate and, consequently, DA release can reverse depending on the average activity level of the Glu afferents to VTA. Further, we propose a mechanism for emergence of transient (phasic) DA peaks and the increase in their frequency in EtOH. Phasic DA transients result from DA neuron population bursts, and these bursts are enhanced in EtOH. These results suggest the role of synchrony and average activity level of Glu afferents to VTA in shaping the phasic and tonic DA release under the acute influence of EtOH and in normal conditions.

neuroscience↗