Disruption of GABAA Receptors on GABAergic Interneurons Leads to Increased Oscillatory Power in the Olfactory Bulb Network

Zoltan Nusser, Leslie M. Kay, Gilles Laurent, Gregg E. Homanics, Istvan Mody
2001 Journal of Neurophysiology  
ics, and Istvan Mody. Disruption of GABA A receptors on GABAergic interneurons leads to increased oscillatory power in the olfactory bulb network. J Neurophysiol 86: [2823][2824][2825][2826][2827][2828][2829][2830][2831][2832][2833] 2001. Synchronized neural activity is believed to be essential for many CNS functions, including neuronal development, sensory perception, and memory formation. In several brain areas GABA A receptor-mediated synaptic inhibition is thought to be important for the
more » ... mportant for the generation of synchronous network activity. We have used GABA A receptor ␤3 subunit deficient mice (␤3Ϫ/Ϫ) to study the role of GABAergic inhibition in the generation of network oscillations in the olfactory bulb (OB) and to reveal the role of such oscillations in olfaction. The expression of functional GABA A receptors was drastically reduced (Ͼ93%) in ␤3Ϫ/Ϫ granule cells, the local inhibitory interneurons of the OB. This was revealed by a large reduction of muscimol-evoked whole-cell current and the total current mediated by spontaneous, miniature inhibitory postsynaptic currents (mIPSCs). In ␤3Ϫ/Ϫ mitral/tufted cells (principal cells), there was a two-fold increase in mIPSC amplitudes without any significant change in their kinetics or frequency. In parallel with the altered inhibition, there was a significant increase in the amplitude of theta (80% increase) and gamma (178% increase) frequency oscillations in ␤3Ϫ/Ϫ OBs recorded in vivo from freely moving mice. In odor discrimination tests, we found ␤3Ϫ/Ϫ mice to be initially the same as, but better with experience than ␤3ϩ/ϩ mice in distinguishing closely related monomolecular alcohols. However, ␤3Ϫ/Ϫ mice were initially better and then worse with practice than control mice in distinguishing closely related mixtures of alcohols. Our results indicate that the disruption of GABA A receptor-mediated synaptic inhibition of GABAergic interneurons and the augmentation of IPSCs in principal cells result in increased network oscillations in the OB with complex effects on olfactory discrimination, which can be explained by an increase in the size or effective power of oscillating neural cell assemblies among the mitral cells of ␤3Ϫ/Ϫ mice.
doi:10.1152/jn.2001.86.6.2823 pmid:11731539 fatcat:gynjsaonibca5j4xyx7lop4q2q