Dynamics of circuit mPFC-DR in a genetic model targeting serotonin transporter

RAPANELLI M; MIGUELEZ FERNÁNDEZ A. M; ZANUTTO B. S; HOMBERG J. ; FRICK L.

San Diego California, USA, Noviembre de 2013.

Congreso; Annual Meeting of the Society for Neuroscience; 2013

Society for Neuroscience

Abstract: The medial prefrontal cortex (mPFC) is one of the main structures that govern complex behaviors. The dorsal raphe nucleus (DR) is one of the major sources of serotonin (5-hydroxytryptamine, 5-HT) in the brain. The DR innervates the mPFC with serotonergic projections. The mPFC projects back to the DR, forming a reciprocal circuit. The aim of this study is to understand the role of 5-HT in the interaction between both brain structures. Therefore, we performed simultaneous electrophysiological recordings in the Slc6a41Hubr strain of rats, which are knockout for the gene of the serotonin transporter (SERT). These animals have reduced basal levels of 5-HT and 5-Hydroxyindoleacetic acid (5-HIAA) levels in the mPFC and the DR, and impaired evoked release of 5-HT in the brain cortex after electrical stimulation. Besides, SERT-KO rats have cognitive deficits that can be attributable to abnormal functioning of the mPFC-DR circuit due to the lack of 5-HT. Animals were deeply anesthetized with uretane and placed in a stereotaxic frame. Two arranges of 3 tetrodes each, were positioned: one in the mPFC (AP = 2.7 mm, L = 1.4 mm, DV = 1.6 mm) and the other one in the DR (AP = 7.8 mm, L = 0 mm, DV = 6.0 mm). The local field potential (LFP) was recorded using one of the contacts in each tetrode. The other contacts recorded the extracellular neuronal activity. Finally the animals were perfused with saline followed by formaldehyde 4% to confirm the position of the tetrodes. We successfully performed simultaneous recordings in the mPFC-DR circuit in 11 animals (WT, HET and KO), identifying dozens of neurons per rat and per brain region. Preliminary analysis suggested hyperactivity of serotonergic neurons in the mPFC of KO rats. This observation is in accordance with the over-activity (c-Fos expression) of the orbitofrontal cortex that was previously reported in these animals. The dynamics of the interaction between the mPFC and the DR are now under study. Disclosures: M. Rapanelli: None. A. Miguelez-Fernandez: None. S. Zanutto: None. J. Homberg: None. L. Frick:None. Keyword(s): SEROTONIN PREFRONTAL CORTEX RAPHE