Biology subjects

Zirpel, F.

Publications and source records attributed to Zirpel, F..

2 recordsLinked to original sources

bioRxiv2024

The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons.

A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neurons selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.

neuroscience↗

bioRxiv2022

Cryptochrome Stabilization Ameliorates Chronic Pain

Physiological and pathological pain exhibits striking diurnal variation, but the underlying mechanisms are largely unknown. We now describe an independent molecular clock in peripheral sensory neurons and satellite glial cells of sensory ganglia. We show that it is the sensory neuron transcription-translation feedback loops (TTFLs) that are responsible for diurnal pain behaviors. This clock regulates diurnal neurophysiological responses to a range of ligands, as well as synaptic activities of primary nociceptors. Furthermore, we find that loss of Cry1 and Cry2, the repressive arm of the core TTFLs, intensifies pain responses associated with increased voltage-gated sodium channel currents. Conversely, stabilization of CRY1 and CRY2 using the small molecule KL001, reduces pain sensitivity. Our results highlight novel opportunities to address chronic pain by directly harnessing circadian mechanisms. One-Sentence SummaryA peripheral pain clock governs daily pain fluctuations, which can be harnessed for treating pain disorders.

neuroscience↗