Adeno-associated virus (AAV)-mediated suppression of Ca2+/calmodulin kinase IV activity in the nucleus accumbens modulates emotional behaviour in mice

Miriam Schneider¹ , Rainer Spanagel¹ , Sheng-Jia Zhang² , Hilmar Bading² and Matthias Klugmann²^,3

¹Central Institute of Mental Health (ZI), Department of Psychopharmacology, J5, 68159 Mannheim, Germany

²Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany

³Department of Physiological Chemistry, University of Mainz, Duesbergweg 6, 55099 Mainz, Germany

author email corresponding author email

BMC Neuroscience 2007, 8:105doi:10.1186/1471-2202-8-105


Published:	3 December 2007

Abstract

Background

Calcium/calmodulin-dependent protein kinase IV (CaMKIV) controls activity-dependent gene transcription by regulating the activity of the cyclic AMP response element binding protein (CREB). This signaling pathway is involved in gating emotional responses in the CNS but previous studies did not address the potential roles of CaMKIV in discrete brain regions. In the present study, we aimed at specifically dissecting the role of CaMKIV in the nucleus accumbens of adult mice.

Results

We used recombinant adeno-associated virus (rAAV)-mediated gene transfer of a dominant-negative CaMKIV variant (rAAV-dnCaMKIV) to inhibit endogenous CaMKIV in the nucleus accumbens. rAAV-dnCaMKIV treated animals were subjected to a battery of tests including, prepulse inhibition of the acoustic startle response, open field, social interaction and anxiety-related behaviour. We found that basal locomotor activity in the open field, and prepulse inhibition or startle performance were unaltered in mice infected with rAAV-dnCaMKIV in the nucleus accumbens. However, anxiogenic effects were revealed in social interaction testing and the light/dark emergence test.

Conclusion

Our findings suggest a modulatory role of CaMKIV in the nucleus accumbens in anxiety-like behaviour but not sensorimotor gating.