Different Inhibitory Modalities Shape Rhythmic Activity Generated by Anterior Cingulate Cortex Networks

Gabriella Panuccio, M. D'Antuono, Alfredo Colosimo, G. Cruccu, Massimo Avoli


Generation of rhythmic activity by neuronal networks may represent the epiphenomenon of pathological conditions that underlie several neurological disorders such as cingulate epilepsy, a type of partial epilepsy affecting the anterior cingulate cortex (ACC), and accompanied by progressive cognitive impairment and psychiatric disturbances. We recently discovered that GABA-mediated neurotransmission plays a pivotal role in the generation and maintenance of epileptiform discharges generated by ACC networks in an acute in vitro model of epilepsy. Here we report that the ACC can generate recurrent network events when maintained in vitro by perfusion with extracellular medium close to physiological conditions. Field potential and intracellular recordings from the ACC were performed using coronal brain slices obtained from young-adult rats. When slices were superfused with normal medium, we could observe the generation of synchronous network-driven events occurring at ~0.15 Hz. Simultaneous field potential and intracellular recordings demonstrated that this activity corresponded to synaptic depolarizations. We sought to determine the role of GABAergic network activity in the generation of these spontaneous events. Therefore, we performed pharmacological manipulations that interfere with interneuron function and found that activation of mu-opioid receptors, which are known to control GABA release from presynatic terminals, significantly decreased bursting activity in ACC neurons while slowing down the occurrence of spontaneous network events. In addition similar effects were observed during application of gap junction decouplers. In conclusion, our findings demonstrate that ACC networks generate synchronous events that result in part from interneuron synchronization through gap junctions. We propose that this inhibitory drive may promote and sustain cortical rhythmic activity.


Anterior cingulate cortex; interneurons; gap junctions; mu-opioid receptors

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