Molecular and functional heterogeneity of neural circuits: an example from the olfactory bulb.

In 1875 Camillo Golgi published his classical description of the olfactory bulb, which contained the first images of neurons visualized with the "black reaction". This new staining method opened the way for structural investigations of the nervous tissue, that culminated in the extraordinary neuroanatomical work of Ramón y Cajal and the formulation of the neuron doctrine. Later developments in neurochemical techniques have revealed an astonishing diversity of neural circuits at the molecular level. This essay reflects on the physiological importance of the molecular heterogeneity of synaptic connections. Dendrodendritic circuits of the olfactory bulb will serve as a case for illustrating the relation between molecular composition and functional properties. Specifically, I will consider how the differential expression of GABA(A) receptor subtypes shapes dendrodendritic inhibition and influences olfactory bulb network activities. A concept emerging from recent investigations is that the molecular diversity of GABAergic systems supports neural circuit operations under an extensive range of behavior-dependent network states. Considering the great molecular diversity of synaptic connections, it is useful to reflect on the importance of high-resolution immunohistochemical analyses as a tool for investigating the structural and functional architecture of neural circuits.