Opioid-based drugs remain important tools for the management of pain; however, their reinforcing properties and the development of tolerance and dependence contribute to their misuse and the development of substance use disorders. A major focus of our research is understanding how repeated opioid exposure alters the function of neural circuits that regulate reward, motivation, decision-making, and behavioral control. In parallel, we investigate how chronic psychosocial stress modifies many of these same circuits, contributing to cognitive dysfunction and increasing vulnerability to maladaptive behavior.
A central focus of this work is the prefrontal cortex and nucleus accumbens鈥攖wo highly interconnected brain regions critical for cognitive control and motivated behavior. Using ex vivo brain slice electrophysiology, we examine how chronic drug exposure and stress alter excitatory and inhibitory synaptic transmission, intrinsic neuronal excitability, presynaptic neurotransmitter release, and postsynaptic glutamate receptor signaling. These studies allow us to identify adaptations within specific neuronal populations and determine how disruptions in the balance between excitatory and inhibitory signaling contribute to altered circuit function.
Our laboratory uses a multi-level experimental approach to connect changes at individual synapses and cells to neural circuit activity and behavior. Rodent models of drug self-administration, relapse, chronic stress, and cognitive function are combined with ex vivo electrophysiology, cell- and circuit-specific viral strategies, optogenetics, and in vivo calcium imaging. These approaches allow us to monitor the activity of defined neuronal populations during behavior, identify adaptations within specific neural pathways, and experimentally manipulate these circuits to determine their causal contributions to behavioral outcomes.
Ultimately, our goal is to understand how chronic drug exposure and stress reshape prefrontal-striatal circuits over time, how factors such as biological sex influence vulnerability or resilience to these adaptations, and whether targeted manipulation of specific cells, synapses, or circuits can restore healthy neural and behavioral function.
Kokane SS, Atwell SI, Madayag AC, Anderson EM, Demis S, Engelhardt A, Friedrich L, Hearing MC. Front Cell Neurosci. 2026 May 8;20:1833214. PMID: 42222059
C么t茅 BE, Grafelman EM, Moster L, Zimolzak K, Hix HE, Cooper M, Padula GN, Wheeler DS, Hearing MC, Mantsch JR, Wheeler RA. Front Neurosci. 2026 Jul 13;20:1881674. PMID: 42516549
Grafelman EM, C么t茅 BE, Vlach L, Geise E, Padula GN, Wheeler DS, Hearing M, Mantsch J, Wheeler RA. Neuropsychopharmacology. 2025 Aug;50(9):1376-1384. PMID: 40205012
Navarro G, Rea W, Quiroz C, Moreno E, Gomez D, Wenthur CJ, Casad贸 V, Leggio L, Hearing MC, Ferr茅 S. J Neurosci. 2022 Feb 9;42(6):940-953. PMID: 34876469
Doncheck EM, Anderson EM, Konrath CD, Liddiard GT, DeBaker MC, Urbanik LA, Hearing MC, Mantsch JR.J Neurosci. 2021 Jun 16;41(24):5303-5314. PMID: 33879537
Anderson EM, Loke S, Wrucke B, Engelhardt A, Demis S, O'Reilly K, Hess E, Wickman K, Hearing MC. Neuropsychopharmacology. 2021 Nov;46(12):2158-2169. PMID: 34158613
Anderson EM, Demis S, D'Acquisto H, Engelhardt A, Hearing M. Front Behav Neurosci. 2021 Mar 26;15:621751. PMID: 33841107
Anderson EM, Demis S, Wrucke B, Engelhardt A, Hearing MC. Physiol Behav. 2021 Dec 1;242:113597. PMID: 34536435
Hurley MM, Anderson EM, Chen C, Maunze B, Hess EM, Block ME, Patel N, Cooper Z, McCoy R, Dabra T, Conley W, Reilly MJ, Hearing M, Choi S. Neuroendocrinology. 2020;110(3-4):271-281.PMID: 31167202
Madayag AC, Gomez D, Anderson EM, Ingebretson AE, Thomas MJ, Hearing MC. Brain Struct Funct. 2019 Sep;224(7):2311-2324. PMID: 31201496
Benneyworth MA, Hearing MC, Asp AJ, Madayag A, Ingebretson AE, Schmidt CE, Silvis KA, Larson EB, Ebner SR, Thomas MJ. J Neurosci. 2019 Jun 12;39(24):4785-4796. PMID: 30948476
Hearing M, Jedynak J, Ebner RS, Ingebretson, A, Asp AJ, Fischer RA, Schmidt C, Larson EB, Thomas MJ (2016) Reversal of morphine-induced cell-type specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement. Proc Natl Acad Sci 113(3):757-762.
Jedynak J1, Hearing M1, Kelly M, Ingebretson AE, Fischer R, Ebner SR, Thomas MJ (2016) Cocaine and amphetamine induce overlapping but distinct patterns of AMPAR plasticity in nucleus accumbens medium spiny neurons. Neuropsychopharm 41(2):464-476. 1authors contributed equally
Hearing M, Kotecki L, Marron Fernandez de Velasco E, Fajardo-Serrano A, Luj谩n R, Wickman K (2013) Repeated cocaine weakens GABAB-Girk signaling in Layer 5/6 pyramidal neurons in the prelimbic cortex. Neuron 80(1): 159-170.
