Projects

Cortical circuits for sensory predictive coding and the generation of prediction errors

Sensory processing in the cerebral cortex is significantly modulated by context. Interactions among top-down, bottom-up, and local neuronal connections serve to modulate the processing of sensory inputs based on experienced context. This modulation involves the reduction of responses to predictable stimuli (e.g. repetition suppression) and enhancement of neuronal responses to unexpected stimuli (e.g. “prediction errors”), which then update circuit connections to dynamically shape how an individual perceives and acts on the sensory world.  Though basic, this rapid, dynamic modulation is critical for survival. Further, people with major psychotic diseases like schizophrenia exhibit  aberrant “prediction error” responses to unexpected stimuli, as indexed by the EEG – based “mismatch negativity” biomarker. Currently, the essential cortical circuitry underlying the generation of sensory prediction error is unknown. 

The Hamm lab harnesses circuit neuroscience tools such as optogenetics, two-photon calcium imaging,  and extracellular electrophysiology in awake mice to provide a comprehensive understanding of how cortical circuits, both local and interregional, encode context to modulate processing of incident stimuli. Projects address how glutamatergic inputs from the prefrontal cortex vs acetylcholinergic inputs from the basal forebrain modulate sensory cortices at various circuit levels.  Special focus will be put on local interneuron subpopulations and interlaminar dynamics within visual and auditory cortices, as well as neuro-oscillatory signatures of prediction errors which at once deepen our understanding of circuit dynamics as well as serve as translational hooks for relating findings in rodents to human EEG measurements in a clinical setting.  Results from this project will provide novel insights for future precision treatments of schizophrenia.

see: Hamm, J.P., Yuste, R. (2016). Somatostatin Interneurons Control a Key Component of Mismatch Negativity in Mouse Visual Cortex. Cell Reports. 16, 407–420.

Ross, J.M., Hamm, J.P. (2020) Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents. Front Neural Circuits14:13

Hamm, J.P., Shymkiv, Y., Han, S., Yang, W. Yuste, R. (2021) Cortical ensembles selective for context. PNAS.  

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Current funding:
Fronto-sensory circuit mechanisms of perceptual novelty processing“, NIMH R00-MH115082, PI: J.P. Hamm ($250,000/year total)

“Mapping the role of basal forebrain projections to visual cortex in novelty processing”, Whitehall Foundation, PI: J.P. Hamm ($75,000/year direct)

“Transcriptomic Profiling of a Novel Subtype of Cortical Neurons Selective for Sensory Prediction Errors”, Brain and Behavior Research Foundation (BBRF) Young Investigator Grant (NARSAD; 2 years; $35,000 per year, direct).

Neural circuits and schizophrenia

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