The prefrontal cortex (PFC) is pivotal to the integration and coordination of information internally generated and received from the external world. PFC is most important when behavior must be guided by internal intentions (often referred to as goal-directed behavior), and in line with this the PFC is required for cognitive processes such as attention, working memory, planning and decision-making. Disturbed prefrontal functioning underlies many cognitive and behavioral disturbances associated with neuropsychiatric disorders such schizophrenia, ADHD, autism and drug-addiction.
Proper cognitive functions are essential for most aspects in our everyday life and extensive evidence exists that cognition is associated with synchronization of neuronal activity within and between brain areas. We and others have shown that synchronous brain activity relies on an intricate interplay between excitation and inhibition. The inhibitory interneurons expressing parvalbumin (PV) are key players in the generation of synchronous brain activity in the gamma range (30-80 Hz), and increases in cortical gamma oscillations is a well-documented signature of cognitive processing. Importantly, deficits in PV neurons and impaired prefrontal gamma oscillations have repetitively been connected to cognitive deficits in neuropsychiatric disorders.
Normal network functions in cognition
With electrophysiological recordings, optogenetic manipulations and imaging in behaving mice and rats we are probing the contribution of specific neuronal subtypes to cognitive functions. We are especially interested in the PFC circuitry and circuitry giving direct input to mPFC, including the raphe nuclei, thalamus and the cholinergic space. We are also investigated how the PFC influences processing in cortical sensory areas.
Our research is formulated from the firm belief that only experiments in relation to behavioral functions can directly address when and how the brain's circuits exert their unique actions.
Mechanisms underlying psychiatric disorders
Ongoing research in the lab aims to understand how brain activity and neuronal networks are affected or altered in psychiatric disorders such as schizophrenia. We are using transgenic animals modeling aspects of mental disorders as well as pharmacology and optogenetics to decipher how changed brain activity relate to changes in behavior.
Therapies for mental disorders
The ultimate goal for our research is to identify novel, and specific, cellular and molecular targets for pharmacological interventions in psychiatric disorders.
Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity.
Proc. Natl. Acad. Sci. U.S.A. 2016 Jan;113(4):822-9
Loss of cyclin-dependent kinase 5 from parvalbumin interneurons leads to hyperinhibition, decreased anxiety, and memory impairment.
J. Neurosci. 2015 Feb;35(6):2372-83
A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei.
Neuron 2014 Aug;83(3):663-78
A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior.
Mol. Psychiatry 2012 May;17(5):537-48
Complete list of publications
Mikael Corell - Senior Lab manager
Xinming Wang - PhD student
Yang Xuan - PhD student
Hoseok Kim - Senior Researcher
Sofie Ährlund-Richter - PhD student
Nicolas Guyon - PhD student
Niten Olofsson - PhD student
Charlotte Alme - Postdoc
Joseph Clerke - Student