Optical manipulations reveal strong reciprocal inhibition but limited recurrent excitation within olfactory bulb glomeruli.

The local circuitry within olfactory bulb glomeruli filters, transforms, and facilitates information transfer from olfactory sensory neurons to bulb output neurons. Two key elements of this circuit are glutamatergic tufted cells (TCs) and GABAergic periglomerular (PG) cells, both of which actively shape mitral cell activity and bulb output. A subtype of TCs, the external tufted cells (eTCs), can synaptically excite PG cells, but there are unresolved questions about other aspects of the glomerular connections, including the extent of connectivity between eTCs and the precise nature of reciprocal interactions between TCs and PG cells. We combined patch-clamp recordings in OB slices and optophysiological tools to investigate local functional connections within glomeruli of mice and rats. When TCs that express cholecystokinin (CCK) were optically suppressed, excitatory post-synaptic currents (EPSCs) in “uniglomerular” PG cells that extend dendrites to one glomerulus were decreased, consistent with TC activation being required for most excitation of these PG cells. However, TC suppression had no effect on EPSCs in eTCs, arguing that TCs make few, if any, direct glutamatergic synaptic connections onto eTCs. The absence of synaptic connections between eTCs was also supported by recordings in eTC pairs. Lastly, we show using similar optical suppression methods that GAD65-expressing PG cells, mainly uniglomerular cells, provide strong inhibition onto eTCs. Our results imply that the local network of CCK-expressing TCs form potent reciprocal chemical synaptic connections with GAD65-expressing uniglomerular PG cells but not eTCs. This configuration favors local inhibition over recurrent excitation within a glomerulus, limiting its output. Significance Statement The brain circuits involved with the initial processing of sensory information are comprised of networks of excitatory and inhibitory neurons. The strength of local connections can impact the weighting of excitation versus inhibition and determine whether sensory signals are passed on to higher-order brain structures. We investigated the connectivity between excitatory and inhibitory neurons in discrete glomerular structures of the rodent olfactory bulb. We found that excitatory neurons make potent chemical synaptic connections with a class of inhibitory cells with dendrites confined to one glomerulus. However, excitatory cells do not form chemical synaptic connections with each other. This circuit configuration suggests that sensory input is generally biased toward driving more local inhibition than recurrent excitation, thus suppressing bulbar output.