![]() From this meticulous observational work, Cajal hypothesized the role of the different neuronal compartments in information processing. More than a century ago, Santiago Ramon y Cajal provided us with a tremendously extensive description of the various morphologies of the neuronal types constituting the mammalian brain and other species’ nervous systems (Cajal, 1952). Moreover, we discuss how the contribution of dendrites and axons to neuronal excitability may impose constraints on the morphology of these compartments in specific functional contexts. In this article, we present a few examples of “misbehaving” neurons (with a non-canonical polarity scheme) to highlight the diversity of solutions that are used by mammalian neurons to transmit information. In several interneuron types, all functions are carried out by dendrites as these neurons are devoid of a canonical axon. In fact, dendrites can be the site of AP initiation and propagation, and even neurotransmitter release. Even though this canonical division of labor is true for a number of neuronal types in the mammalian brain (including neocortical and hippocampal pyramidal neurons or cerebellar Purkinje neurons), many neuronal types do not comply with this classical polarity scheme. This knowledge is important for understanding complex brain activities in general, but also to improve the treatment of neurological disorders such as DS.Our general understanding of neuronal function is that dendrites receive information that is transmitted to the axon, where action potentials (APs) are initiated and propagated to eventually trigger neurotransmitter release at synaptic terminals. My experience on measuring subcellular axonal functions as well as neuronal network oscillations provides the unique possibility to advance our understanding of the causal relationship between axonal currents, AP signalling and GABAergic inhibition in neuronal networks. So far, other studies were unable to directly resolve the ion channel activity in PV-IN axons of DS mice because of the difficulties in accessing the fine axonal structures. The project aims to identify how axonal functions are impaired in DS mice and to link the axonal deficits to dysfunctions in neuronal network oscillations. These dysfunctions are believed to be caused by changes in action potential (AP) signalling in PV-IN axons. In close agreement, transgenic mice with reduced SCN1A gene expression (DS mice) reproduce key features of DS symptoms and show dysfunctions in parvalbumin-expressing GABAergic interneurons (PV-INs), as well as deficits in cortical network oscillations. Impairments of GABAergic inhibition are known to lead to epilepsy and other cognitive disorders. These inhibitory neurons are responsible for balancing cortical brain activity by the release of the neurotransmitter GABA from their axonal terminals. Most DS patients show a mutation in the SCN1A gene, which encodes for a sodium channel subunit (NaV1.1) highly expressed in axons of cortical GABAergic interneurons. Dravet Syndrome (DS) is a severe form of childhood epilepsy with an early onset (under one year) affecting cognitive development and often causing sudden death. ![]()
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