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In the Olfactory Bulb, Being Normal Goes Against the Norm [Murthy Lab]

In the Olfactory Bulb, Being Normal Goes Against the Norm [Murthy Lab]

Perhaps the first lesson that we learn in any neuroscience course involves defining the unique properties of neurons. Neurons, we learn, are polarised entities where information flows from multiple dendrites via the soma to a single process called the axon, where action potentials are generated at the axon initial segment, and neurotransmitter released at the axonal terminals. Moreover, unlike cells in other tissues, these extremely polarised neurons do not retain the ability to regenerate through life, but are exclusively born during embryonic and early postnatal development.  These defining properties, however, are violated routinely in one part of the brain, which was the subject of our recent paper, published in collaboration with Matt Grubb’s lab at King’s College London.

For interneurons in the mammalian olfactory bulb (OB) – the first area of the brain to process olfactory stimuli – being “a normal neuron” is almost unheard of and the exception has somehow become the rule. Here groups of neurons are known to lack axons completely, opting instead to release neurotransmitter exclusively from their dendrites.  Even more strikingly, most OB interneuron populations retain neurogenic capabilities throughout life.  These regenerating cells include a well-defined group of interneurons that co-release GABA and dopamine at the level of the first synapse from olfactory sensory neurons to bulbar principal cells.  However, our study has shown that this well-defined population actually consists of two completely distinct subpopulations.  The first is ‘normal’ in the context of OB interneurons, because these cells lack an axon and are generated throughout postnatal life via adult neurogenesis.  The second, in contrast, is highly abnormal as far as OB interneurons go but entirely ‘normal’ with respect to the rest of the brain, because these cells have a clearly defined axon and are generated exclusively in early embryonic development.  Moreover, these two dopaminergic cell types have different functional properties: the axon-bearing neurons are more intrinsically excitable than their axon-lacking neighbours, and for certain long-latency responses are more broadly tuned to odour stimuli.

These morphological, physiological and developmental distinctions place important constraints on the functional roles of OB dopaminergic neurons in sensory processing and on their potential for plasticity. In addition, the different phenotypes and potential functions of embryonically- and adult-born neurons call for further investigation of the evolutionary advantage of retaining neurogenic capabilities throughout life. Does being axonless help newly-generated neurons integrate into already-functioning adult circuits?  Are axons only useful to interneurons born before birth?  What are the contributions of each dopaminergic sub-population to olfactory behaviour? And how do both types of neuron adapt to alterations in sensory experience?  Our future work in the Murthy, Grubb and soon-to-be-established Galliano laboratory at the University of Cambridge (UK) aims to address.

Extreme morphological heterogeneity of sparsely-labelled DA neurons, without (top) and with (bottom) an axon. Approximate location of the axon initial segment (AIS) is indicated with a magenta square

by Elisa Galliano 


Venki Murthy faculty profile

Murthy lab website

Elisa Galliano

Elisa Galliano