Cocaine diminishes functional network robustness and destabilizes the energy landscape of neuronal activity in the medial prefrontal cortex

Author:

Borzou Ahmad12ORCID,Miller Sierra N3ORCID,Hommel Jonathan D3ORCID,Schwarz J M14

Affiliation:

1. Department of Physics and BioInspired Institute, Syracuse University , Syracuse, NY 13244 , USA

2. CompuFlair , Houston, TX 77064 , USA

3. Department of Pharmacology and Toxicology, Center for Addiction Sciences and Therapeutics, University of Texas Medical Branch , Galveston, TX 77555 , USA

4. Indian Creek Farm , Ithaca, NY 14850 , USA

Abstract

Abstract We present analysis of neuronal activity recordings from a subset of neurons in the medial prefrontal cortex of rats before and after the administration of cocaine. Using an underlying modern Hopfield model as a description for the neuronal network, combined with a machine learning approach, we compute the underlying functional connectivity of the neuronal network. We find that the functional connectivity changes after the administration of cocaine with both functional-excitatory and functional-inhibitory neurons being affected. Using conventional network analysis, we find that the diameter of the graph, or the shortest length between the two most distant nodes, increases with cocaine, suggesting that the neuronal network is less robust. We also find that the betweenness centrality scores for several of the functional-excitatory and functional-inhibitory neurons decrease significantly, while other scores remain essentially unchanged, to also suggest that the neuronal network is less robust. Finally, we study the distribution of neuronal activity and relate it to energy to find that cocaine drives the neuronal network towards destabilization in the energy landscape of neuronal activation. While this destabilization is presumably temporary given one administration of cocaine, perhaps this initial destabilization indicates a transition towards a new stable state with repeated cocaine administration. However, such analyses are useful more generally to understand how neuronal networks respond to perturbations.

Funder

NCATS

NIDA

NIAAA

Publisher

Oxford University Press (OUP)

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