Neuronal Synchronization and Aminergic Modulation of Network Oscillations – Implications for Schizophrenia
by
André Fisahn(Neuronal Oscillations Laboratory, Karolinska Institute)
→
Europe/Stockholm
RB35
RB35
Description
Recent schizophrenia research has thrown into focus the apparent discrepancy between the reduction of task-driven gamma oscillation activity dominating the human EEG literature and the recently discovered aberrant gamma oscillation-hyperactivity common to animal models and also linked to psychotic symptoms in sporadic human reports. Gamma oscillations (30-80 Hz) are physiological electric activity patterns prevalent in the brain, which are associated with attention, working memory, sensory perception, long-term memory encoding and recall. Importantly, in mental illnesses featuring cognitive disturbances, such as Schizophrenia or Alzheimer’s disease, gamma oscillation characteristics are altered. In particular impaired gamma oscillations are associated with treatment-resistant cognitive deficits in schizophrenia. The correct reproduction of these impairments in animal models offers important new translational opportunities in schizophrenia and neuropsychiatric disorders.
All aspects of cognitive function are regulated by the aminergic systems of the brain, which are also associated with mental disorders. Yet little research has been done to understand how aminergic molecules modulate or control gamma oscillations and whether these modulatory systems might offer targets for therapeutic intervention aimed at adjusting gamma oscillation power.
Using combined extracellular local field potential and intracellular patch clamp recordings in in vitro preparations of the rodent hippocampus we found that aminergic neuromodulation is capable to bi-directionally regulate the power of gamma oscillations in the hippocampus, without affecting the overall firing rate of action potentials. Rather, it is the phase-synchronization of pyramidal cell and fast-spiking interneuron activity that is affected by the activation of histamine H3, dopamine D4 or serotonergic 5HT1A receptors. Our data show that the various schizophrenia hypotheses (dopaminergic, NRG/ErbB4 neurodevelopmental, glutamatergic, GABAergic) may converge on fast-spiking interneurons to influence gamma oscillation levels. This is a potential physiological mechanism by which the gain of signal transmission to downstream targets can be regulated. Targeting this mechanism may have a potential use in future antipsychotic or pro-cognitive pharmaceutical therapy.
