A critical issue within the mental health field is the lack of granularity in diagnostic practices. For example, a patient that is sleeping and eating too much may be prescribed the same antidepressant as a patient who is sleeping and eating too little. This may explain the low rates of efficacy for first line antidepressants and begs further dissection. This underscores the need to find more granularity within mental health conditions and alternative treatment options, which is the scientific vision of the Coley Laboratory.

In the Coley Lab, we apply integrative approaches such as in vivo 2-photon calcium imaging to measure neural activity and population dynamics, and ex vivo electrophysiology to record synaptic properties. We utilize optogenetics techniques to selectively activate neural circuits and assess the response within specific neurons. We also use computer-based tracking systems to monitor behavioral tasks and apply machine learning methods to uncover the relationship between neural activity and behavior. Additionally, we use theoretical and neurocomputational models to further understand neuronal population function in higher-order processing regions.

We study depressive-like phenotypes such as Anhedonia, described as the inability to experience pleasure or hedonic feeling, and a core feature in schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). Anhedonia is linked to a dysregulation within the brain reward pathways that include the prefrontal cortex which is highly involved in emotional and valence processing, critical for encoding hedonic values. It remains unknown how specific neural substrates modulate mPFC valence-specific neuronal population activity during anhedonia.

Key questions remain that would elucidate how a dysregulation in synaptic activity within select brain regions contributes to depressive-like behaviors. 1) For instance, what are the specific neuronal populations and cortical circuits involved in stress-induced depression? Isolating individual neuronal cell-types and pathways are a critical step for targeted therapeutic options. 2) Also, how does a dysregulation of synaptic proteins affect synaptic plasticity during depressive-like phenotypes? Identifying the synaptic proteins of interest would help understand the neuropathophysiological implications within these disorders. 3) Finally, what are the biomarkers that lead to the on-set of SCZ vs. MDD? Providing early intervention in both schizophrenia and major depressive disorder have shown to dramatically reduce psychotic symptoms and suicidal rates, respectively.