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In the olfactory bulb (OB), odorants induce oscillations in the [gamma], range (20-80 Hz) that play an important role in the processing of sensory information. Synaptic transmission between dendrites is a major contributor to this processing. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAergic inhibition back onto mitral cells. Although this reciprocal synapse is thought to be a key element supporting oscillatory activity, the mechanisms by which dendrodendritic inhibition induces and maintains [gamma] oscillations remain unknown. Here, we assessed the role of the dendrodendritic inhibition, using mice lacking the [GABA.sub.A] receptor [alpha]1-subunit, which is specifically expressed in mitral cells but not in granule cells. The spontaneous inhibitory postsynaptic current frequency in these mutants was low and was consistent with the reduction of [GABA.sub.A] receptor clusters detected by immunohistochemistry. The remaining [GABA.sub.A] receptors in mitral cells contained the [alpha]3-subunit and supported slower decaying currents of unchanged amplitude. Overall, inhibitory-mediated interactions between mitral cells were smaller and slower in mutant than in WT mice, although the strength of sensory afferent inputs remained unchanged. Consequently, both experimental and theoretical approaches revealed slower [gamma] oscillations in the OB network of mutant mice. We conclude, therefore, that fast oscillations in the OB circuit are strongly constrained by the precise location, subunit composition and kinetics of [GABA.sub.A] receptors expressed in mitral cells. [alpha]1 knockout | [GABA.sub.A] receptor | olfaction | reciprocal synapses

The production of new neurons in the olfactory bulb (OB) through adulthood is a major mechanism of structural and functional plasticity underlying learning-induced circuit remodeling. The recruitment of adult-born OB neurons depends not only on sensory input but also on the context in which the olfactory stimulus is received. Among the multiple steps of adult neurogenesis, the integration and survival of adult-born neurons are both strongly influenced by olfactory learning. Conversely, optogenetic stimulation of adult-born neurons has been shown to specifically improve olfactory learning and long-term memory. However, the nature of the circuit and the synaptic mechanisms underlying this reciprocal influence are not yet known. Here, we showed that olfactory learning increases the spine density in a region-restricted manner along the dendritic tree of adult-born granule cells (GCs). Anatomical and electrophysiological analysis of adult-born GCs showed that olfactory learning promotes a remodeling of both excitatory and inhibitory inputs selectively in the deep dendritic domain. Circuit mapping revealed that the malleable dendritic portion of adult-born neurons receives excitatory inputs mostly from the regions of the olfactory cortex that project back to the OB. Finally, selective optogenetic stimulation of olfactory cortical projections to the OB showed that learning strengthens these inputs onto adult-born GCs. We conclude that learning promotes input-specific synaptic plasticity in adult-born neurons, which reinforces the top-down influence from the olfactory cortex to early stages of olfactory information processing. [ABSTRACT FROM AUTHOR]

In the olfactory bulb (OB), odorants induce oscillations in the γ range (20-80 Hz) that play an important role in the processing of sensory information. Synaptic transmission between dendrites is a major contributor to this processing. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAergic inhibition back onto mitral cells. Although this reciprocal synapse is thought to be a key element supporting oscillatory activity, the mechanisms by which dendrodendritic inhibition induces and maintains γ oscillations remain unknown. Here, we assessed the role of the dendrodendritic inhibition, using mice lacking the GABAA receptor α1-subunit, which is specifically expressed in mitral cells but not in granule cells. The spontaneous inhibitory postsynaptic current frequency in these mutants was low and was consistent with the reduction of GABAA receptor clusters detected by immunohistochemistry. The remaining GABAA receptors in mitral cells contained the α3-subunit and supported slower decaying currents of unchanged amplitude. Overall, inhibitory-mediated interactions between mitral cells were smaller and slower in mutant than in WT mice, although the strength of sensory afferent inputs remained unchanged. Consequently, both experimental and theoretical approaches revealed slower γ oscillations in the OB network of mutant mice. We conclude, therefore, that fast oscillations in the OB circuit are strongly constrained by the precise location, subunit composition and kinetics of GABAA receptors expressed in mitral cells. [ABSTRACT FROM AUTHOR]