Oxytocin in the prefrontal cortex: from neuromodulation of the local circuit to fear extinction

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The hypothalamic neuropeptide oxytocin plays an important role in modulation of synaptic transmission in various brain regions, including the cortex.

In this project we will study how OT influences activity of neuronal ensembles in the rodent medial prefrontal cortex, mPFC.

Using viral, genetic, optogenetic and electrophysiology, we will evoke endogenous OT release to monitor microcircuit activity in the mPFC in vitro and in vivo with subsequent behavioural analysis. The central hypotheses of our project is that OT directly or indirectly activates principle neurons of the mPFC facilitating, in turn, extinction of negative (i.e. fear) memory. The testing this hypothesis will be achieved in various in vitro and in vivo experimental setups, using electrophysiology, viral, anatomical, optogenetic and behavioural approaches.
Eliava, M., Melchior, M., Knobloch-Bollmann, H.S., Wahis, J., da Silva Gouveia, Tang, Y., Ciobanu, A.C., Triana del Rio, R., Roth, L.C., Althammer, F., Chavant, V., Goumon, Y., Gruber, T., Busnelli, M., Chini, B., Tan, L., Mitre, M., Froemke, R.C., Chao, M.V., Giese, G., Sprengel, R., Kuner, R., Poisbeau, P., Seeburg, P.H., Stoop, R., Charlet, A., Grinevich V. A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing. Neuron 2016 (in press); http://dx.doi.org/10.1016/j.neuron.2016.01.041

Madroñal, N., Delgado-García, J.M., Fernández-Guizán, A., Chatterjee, J., Köhn, M., Mattucci, C., Jain, A., Tsetsenis, T., Illarionova, A., Grinevich, V., Gross, C.T., Gruart, A. Rapid erasure of hippocampal learning and plasticity following transient blockade of dentate gyrus granule cells. Nat. Commun. 2016 (in press). 

Knobloch S, Charlet A, Stoop R, Grinevich V (2014) Viral vectors for optogenetics of hypotha- lamic neuropeptides. Springer Protocol Book on “Viral Vectors in Neurobiology and Brain Diseases”, Series on “Neuromethods” 82:311-330.

Knobloch S, Grinevich V (2014) Evolution of central oxytocin pathways in vertebrates. Front Behav Neurosci 8:31.

Silva BA, Mattucci C, Krzywkowski P, Murana E, Illarionova A, Grinevich V, Canteras NS, Ragozz- ino D, Gross CT (2013) Independent hypothalamic circuits for social and predator fear. Nat Neurosci 12:1731-1733.

Knobloch S, Charlet A, Hoffmann LC, Eliava M, Khrulev S, Cetin AH, Osten P, Schwarz MK, Seeburg PH, Stoop R, Grinevich V (2012) Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73:553-566.

Sivukhina EV, Morozov IuE, Dolzhikov AA, Jirikowski GF, Grinevich V (2010) Comparison of vasopressin and oxytocin expressions in the hypothalamo-neurohypophysial system of patients with chronic heart failure. Horm Metab Res 42:56-61.

Grinevich V, Kolleker A, Eliava M, Takada N, Takuma H, Fukazawa Y, Shigemoto R, Kuhl D, Wa- ters J, Seeburg PH, Osten P (2009) TgArc/Arg3.1-d4EGFP indicator mice: a versatile tool to study brain activity changes in vitro and in vivo. J Neurosci Meth 184:25-36.

Broser PJ, Grinevich V, Osten P, Sakmann B, Wallace DJ (2008) Critical period plasticity of axonal arbours of layer 2/3 pyramidal neurons in rat somatosensory cortex: layer specific reduction of projections into deprived cortical columns. Cereb Cortex 18: 1588-1603.

Grinevich V, Brecht M, Osten P (2005) Monosynaptic pathway from rat vibrissa motor cortex to facial motor neurons revealed by lentivirus-based axonal tracing. J Neurosci 25:8250- 8258.

*Principal investigators of other projects within the CRC