Biology subjects

Sadikot, A.

Publications and source records attributed to Sadikot, A..

3 recordsLinked to original sources

bioRxiv2020

Paranode stability requires UNC5B expression by oligodendrocytes

In the mature CNS, netrin-1 is expressed by neurons and oligodendrocytes and implicated in the stability of axo-oligodendroglial paranodal junctions. Here we report that the netrin receptor UNC5B is highly expressed by mature oligodendrocytes and enriched at paranodes. We demonstrate that paranodes become disorganized following conditional deletion of UNC5B in oligodendrocytes, with disruption of the interface between glial loops and detachment of loops from the axon. As a result, Caspr1 and Kv1.1 disperse along the axon, internodes fail to lengthen and compact myelin periodicity is reduced. Paranodal and axoglial domain disorganization progressively worsens and a delay in motor learning develops in aged mice lacking oligodendroglial UNC5B. Altered glial loop ultrastructure and reduced levels of claudin-11 and JAM-C tight junction proteins support the conclusion that disruption of autotypic junctions between paranodal loops underlies paranode disorganization. Our findings reveal an essential contribution of oligodendroglial UNC5B at paranodes that is required for the stability of mature myelin.

neuroscience↗

bioRxiv2019

The Role of the Subthalamic Nucleus in Inhibitory Control of Oculomotor Behavior in Parkinson’s Disease

The ability to inhibit an inappropriate action in a context is an important part of the human cognitive repertoire, and deficiencies in this ability are common in neurological and psychiatric disorders. An anti-saccade is a simple experimental task within the oculomotor repertoire that can be used to test this ability. The task involves an inhibition of a saccade to the peripheral target (pro-saccade) and generation of a voluntary eye movement toward the mirror position (anti-saccade). Previous studies provide evidence for a possible contribution from the basal ganglia in anti-saccade behavior. However, the precise role of different components in generation of anti-saccade behavior is still uncertain. Parkinsons disease patients with implanted deep brain stimulation (DBS) in subthalamic nucleus (STN) provide us with a unique opportunity to investigate the role of STN in anti-saccade behavior. Previous attempts to show the effect of STN DBS on anti-saccades have produced conflicting observations. For example, the effect of STN DBS on anti-saccade error rate is not yet clear. Part of this inconsistency may be related to differences in dopaminergic states in different studies. Here, we tested Parkinsons disease patients on anti- and pro-saccade tasks ON and OFF STN DBS and ON and OFF dopaminergic medication. We made three main observations. First, STN DBS increases the anti-saccade error rate while patients are OFF dopamine replacement therapy. Second, there is an interaction between dopamine replacement therapy and STN DBS. More specifically, L-dopa reduces the effect of STN DBS on anti-saccade error rate. Third, STN DBS can induce different effects on pro- and anti-saccades in different patients. These observations provide evidence for an important role for the STN in the circuitry underlying context-dependent modulation of visuomotor action selection.

neuroscience↗

bioRxiv2018

Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain.

Netrin-1 was initially characterized as an axon guidance molecule that is essential for normal embryonic neural development; however, many types of neurons continue to express netrin-1 in the post-natal and adult mammalian brain. Netrin-1 and the netrin receptor DCC are both enriched at synapses. In the adult hippocampus, activity-dependent secretion of netrin-1 by neurons potentiates glutamatergic synapse function, and is critical for long-term potentiation, an experimental cellular model of learning and memory. Here, we assessed the impact of neuronal expression of netrin-1 in the adult brain on behavior using tests of learning and memory. We show that adult mice exhibit impaired spatial memory following conditional deletion of netrin-1 from glutamatergic neurons in the hippocampus and neocortex. Further, we provide evidence that mice with conditional deletion of netrin-1 do not display aberrant anxiety-like phenotypes and show a reduction in self-grooming behaviour. These findings reveal a critical role for netrin-1 expressed by neurons in the regulation of spatial memory formation.

neuroscience↗