Search bioRxiv⌕ Search

Biology subjects

Abdelaziz, A.

Publications and source records attributed to Abdelaziz, A..

2 recordsLinked to original sources

The developmental timing of spinal touch processing alterations and its relation to ASD-associated behaviors in mouse models

Altered somatosensory reactivity is frequently observed among individuals with autism spectrum disorders (ASDs). Here, we report that while multiple mouse models of ASD exhibit aberrant somatosensory behaviors in adulthood, some models exhibit altered tactile reactivity as early as embryonic development, while in others, altered reactivity emerges later in life. Additionally, tactile over-reactivity during neonatal development is associated with anxiety-like behaviors and social interaction deficits in adulthood, whereas tactile over-reactivity that emerges later in life is not. The locus of circuit disruption dictates the timing of aberrant tactile behaviors: altered feedback or presynaptic inhibition of peripheral mechanosensory neurons leads to abnormal tactile reactivity during neonatal development, while disruptions in feedforward inhibition in the spinal cord lead to touch reactivity alterations that manifest later in life. Thus, the developmental timing of aberrant touch processing can predict the manifestation of ASD-associated behaviors in mouse models, and differential timing of sensory disturbance onset may contribute to phenotypic diversity across individuals with ASD.

neuroscience↗

DRG afferents that mediate physiologic and pathologic mechanosensation from the distal colon

The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal disease. Here, we report genetically defined subsets of colon innervating DRG neurons with diverse morphologic and physiologic properties. Four colon innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous mechanoreceptor populations, colon innervating DRG afferents exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon innervating HTMRs mediate pathophysiological responses to colon distension revealing a target population for therapeutic intervention.

neuroscience↗