Dr. Matthew Hearing's Research

Opioid-based drugs are mainstays for pain management. However, side effects such as euphoria and the development of tolerance and dependence contribute to an increasing diversion of these readily available compounds for non-therapeutic use. A major emphasis in my research is using ex vivo brain slice electrophysiology to study how repeated opiate exposure modifies glutamate and gamma-Aminobutyric Acid (GABA)-mediated synaptic strength in neurons of the prefrontal cortex and nucleus accumbens – two highly inter-connected brain regions involved in decision-making and reward. Current studies focus on identifying alterations in intrinsic cell membrane properties (i.e., excitability), presynaptic glutamate release and postsynaptic signaling mediated by ionotropic AMPA- and NMDA-type glutamate receptors in medium spiny neurons and pyramidal cells -- the two principal cell-types in the nucleus accumbens and prefrontal cortex respectively. Additional studies focus on drug-induced adaptations in prefrontal cortex inhibitory signaling mediated by GABA and dopamine and how these modifications alter activation of layer 5/6 pyramidal neurons.

Research in my laboratory primarily employs a model of drug self-administration in mice genetically altered to express fluorescent proteins in specific sub-populations of neurons. This behavioral approach is used in combination with slice electrophysiology and utilizes genetic incorporation of light-sensitive ion channels (optogenetics) and retrograde neuron-tract tracers that allows us to isolate discrete forms of plasticity occurring within select neural circuits. We also use in vivo optogenetic stimulation to modulate synaptic strength in order to assess the functional role these adaptations play in driving relapse and identify targets for pharmacotherapies aimed at mitigating this behavior.

A second research interest in my laboratory integrates electrophysiology, rodent models of cognitive flexibility, and a neurodevelopmental model of schizophrenia to examine changes in prefrontal cortex pyramidal neuron and GABAergic interneuron signaling in hopes of identifying cellular correlates of prefrontal cortical dysfunction responsible for cognitive impairments observed in neuropsychiatric disorders.

Selected Publications