Dr. Matthew Hearing's Research
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—two 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.
Selected Publications
Link to all Dr. Hearing's Publications
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Kokane SS, Atwell SI, Madayag AC, Anderson EM, Demis S, Engelhardt A, Friedrich L, Hearing MC. Remifentanil self-administration promotes circuit- and sex-specific adaptations within the prefrontal-accumbens pathways.Front Cell Neurosci. 2026 May 8;20:1833214. PMID: 42222059
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Côté BE, Grafelman EM, Moster L, Zimolzak K, Hix HE, Cooper M, Padula GN, Wheeler DS, Hearing MC, Mantsch JR, Wheeler RA. Nucleus accumbens DRD2 receptor agonism attenuates escape behavior. Front Neurosci. 2026 Jul 13;20:1881674. PMID: 42516549
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Grafelman EM, Côté BE, Vlach L, Geise E, Padula GN, Wheeler DS, Hearing M, Mantsch J, Wheeler RA. Aversion-induced drug taking and escape behavior involve similar nucleus accumbens core dopamine signaling signatures. Neuropsychopharmacology. 2025 Aug;50(9):1376-1384. PMID: 40205012
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Navarro G, Rea W, Quiroz C, Moreno E, Gomez D, Wenthur CJ, Casadó V, Leggio L, Hearing MC, Ferré S. Complexes of Ghrelin GHS-R1a, GHS-R1b, and Dopamine D1 Receptors Localized in the Ventral Tegmental Area as Main Mediators of the Dopaminergic Effects of Ghrelin. J Neurosci. 2022 Feb 9;42(6):940-953. PMID: 34876469
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Estradiol Regulation of the Prelimbic Cortex and the Reinstatement of Cocaine Seeking in Female Rats. 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
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Anderson EM, Loke S, Wrucke B, Engelhardt A, Demis S, O'Reilly K, Hess E, Wickman K, Hearing MC. Suppression of pyramidal neuron G protein-gated inwardly rectifying K+ channel signaling impairs prelimbic cortical function and underlies stress-induced deficits in cognitive flexibility in male, but not female, mice. Neuropsychopharmacology. 2021 Nov;46(12):2158-2169. PMID: 34158613
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Anderson EM, Demis S, D'Acquisto H, Engelhardt A, Hearing M.The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice. Front Behav Neurosci. 2021 Mar 26;15:621751. PMID: 33841107
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Anderson EM, Demis S, Wrucke B, Engelhardt A, Hearing MC. Infralimbic cortex pyramidal neuron GIRK signaling contributes to regulation of cognitive flexibility but not affect-related behavior in male mice. Physiol Behav. 2021 Dec 1;242:113597. PMID: 34536435
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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. Acute Blockade of PACAP-Dependent Activity in the Ventromedial Nucleus of the Hypothalamus Disrupts Leptin-Induced Behavioral and Molecular Changes in Rats. Neuroendocrinology. 2020;110(3-4):271-281.PMID: 31167202
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Madayag AC, Gomez D, Anderson EM, Ingebretson AE, Thomas MJ, Hearing MC. Cell-type and region-specific nucleus accumbens AMPAR plasticity associated with morphine reward, reinstatement, and spontaneous withdrawal. Brain Struct Funct. 2019 Sep;224(7):2311-2324. PMID: 31201496
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Benneyworth MA, Hearing MC, Asp AJ, Madayag A, Ingebretson AE, Schmidt CE, Silvis KA, Larson EB, Ebner SR, Thomas MJ. Synaptic Depotentiation and mGluR5 Activity in the Nucleus Accumbens Drive Cocaine-Primed Reinstatement of Place Preference. J Neurosci. 2019 Jun 12;39(24):4785-4796. PMID: 30948476
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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.
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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
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Hearing M, Kotecki L, Marron Fernandez de Velasco E, Fajardo-Serrano A, Luján 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.