Biology subjects

Köhr, G.

Publications and source records attributed to Köhr, G..

2 recordsLinked to original sources

bioRxiv2020

A common molecular mechanism for cognitive deficits and craving in alcoholism

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism.

neuroscience↗

bioRxiv2020

Coordinated prefrontal state transition leads extinction of reward-seeking behaviors

Extinction learning suppresses conditioned reward responses and is thus fundamental to adapt to changing environmental demands and to control excessive reward seeking. The medial prefrontal cortex (mPFC) monitors and controls conditioned reward responses. Using in vivo multiple single-unit recordings of mPFC we studied the relationship between single-unit and population dynamics during different phases of an operant conditioning task. To examine the fine temporal relation between neural activity and behavior, we developed a model-based statistical analysis that captured behavioral idiosyncrasies. We found that single-unit responses to conditioned stimuli changed throughout the course of a session even under stable experimental conditions and consistent behavior. However, when behavioral responses to task contingencies had to be updated during the extinction phase, unit-specific modulations became coordinated across the whole population, pushing the network into a new stable attractor state. These results show that extinction learning is not associated with suppressed mPFC responses to conditioned stimuli, but is driven by single-unit coordination into population-wide transitions of the animals internal state.

neuroscience↗