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Hornberg, H.

Publications and source records attributed to Hornberg, H..

2 recordsLinked to original sources

Touch sensation requires the mechanically-gated ion channel Elkin1.

The slightest touch to the skin initiates tactile perception that is almost immediate1. The extraordinary speed of touch perception is enabled by mechanically-activated ion channels, the opening of which excites the endings of sensory neurons innervating the skin to initiate sensation. Here we identify a new mechanically-activated ion channel, Elkin12, that, when ablated in mice, leads to a profound behavioural touch insensitivity. Touch insensitivity in Elkin1-/- mice was caused by a loss of mechanically-activated currents (MA-currents) in around half of all sensory neurons that are activated by light touch (low threshold mechanoreceptors, LTMRs). Reintroduction of Elkin1 into sensory neurons from Elkin1-/- mice acutely restored MA-currents. Piezo23-6 is an established mechanosensitive ion channel required for touch sensation. In mice genetic ablation of Piezo2 renders many, but not all, LTMRs insensitive to mechanical force4,5,7. Here we show that Elkin1 underpins PIEZO2-independent touch sensation. Additionally, we find that Elkin1 is present in many nociceptive sensory neurons which detect potentially damaging and painful mechanical force. These nociceptors depend on Elkin1 for effectively communicating information on sustained noxious mechanical forces. We further identified molecular and functional interactions between the known mechanotransduction protein Stoml38,9 and Elkin1 ion channels. Our data identify Elkin1 as a novel core component of touch transduction in mammals. The specific sensory deficits exhibited by Elkin1-/- mice make Elkin1 a highly desirable target that could be harnessed to treat somatic sensory disorders including pain.

neuroscience↗

Neuronal signature of social novelty exploration in the VTA: implication for Autism Spectrum Disorder

Novel stimuli attract our attention, promote exploratory behavior, and facilitate learning. Atypical habituation and aberrant novelty exploration have been related with the severity of Autism Spectrum Disorders (ASD) but the underlying neuronal circuits are unknown. Here, we report that dopamine (DA) neurons of the ventral tegmental area (VTA) promote the behavioral responses to novel social stimuli, support preference for social novelty, and mediate the reinforcing properties of novel social interaction. Social novelty exploration is associated with the insertion of calcium-permeable GluA2-lacking AMPA-type glutamate receptors at excitatory synapses on VTA DA neurons. These novelty-dependent synaptic adaptations only persist upon repeated exposure to social stimuli and sustain social interaction. Global or DA neuron-specific inactivation of the ASD risk gene Neuroligin3 alters both social novelty exploration and the reinforcing properties of social stimuli. These behavioral deficits are accompanied by an aberrant expression of non-canonical GluA2-lacking AMPA-receptors at excitatory synapses on VTA DA neurons and an occlusion of novelty-induced synaptic plasticity. Altogether, these findings causally link impaired novelty exploration in an ASD mouse model to VTA DA circuit dysfunction.

neuroscience↗