Abstract
Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. We interfered with GABAergic inhibition of mitral and tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal. In these mice, the resulting increase in the intracellular Cl− concentration nearly abolished GABA-induced hyperpolarization of mitral cells (MCs) and unexpectedly increased the number of perisomatic synapses on MCs. In vivo analysis of odorant-induced OB electrical activity revealed increased M/T cell firing rate, altered phasing of action potentials in the breath cycle and disrupted separation of odour-induced M/T cell activity patterns. Mice also demonstrated a severely impaired ability to discriminate chemically similar odorants or odorant mixtures. Our work suggests that precisely tuned GABAergic inhibition onto M/T cells is crucial for M/T cell spike pattern separation needed to distinguish closely similar odours.
Highlights
Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination
We investigated the impact of GABAergic inhibition of M/T cells, a crucial relay station in the OB, on the local circuitry involved in the processing of olfactory information
Regulation of GABAergic input to M/T cells plays a role for odour discrimination in mice[8,9,10]
Summary
Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. The OB is the first relay station of olfactory information in the central nervous system where odour-specific excitatory input from olfactory sensory neurons (OSNs) is received by glutamatergic mitral and tufted cells (M/T cells). The temporal component involves synchronously spiking mitral cells (MCs), reflected by g-frequency oscillations[10,18,19], as well as separation of M/T cell activity pattern over time[20,21,22] Both types of coding depend on GABAergic inhibition[4,10,21,23]. Discrimination of similar odours or of odour mixtures seems to be influenced by the strength of inhibitory input from GCs, the predominant interneuron type in the OB This conclusion was supported by experiments that changed GC activity with genetic, pharmacological or optogenetic tools[8,9,10,24]. Changing the electrical excitability of GCs by disrupting specific glutamate receptor subunits with Cre-recombinase encoding viruses influenced the time needed for odour discrimination without affecting discrimination accuracy[8]
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