Thalamic NMDA Receptor Function Is Necessary for Patterning of the Thalamocortical Somatosensory Map and for Sensorimotor Behaviors

Abstract

NMDARs play a major role in patterning of topographic sensory maps in the brain. Genetic knock-out of the essential subunit of NMDARs in excitatory cortical neurons prevents whisker-specific neural pattern formation in the barrel cortex. To determine the role of NMDARs en route to the cortex, we generated sensory thalamus-specific NR1 (Grin1)-null mice (ThNR1KO). A multipronged approach, using histology, electrophysiology, optical imaging, and behavioral testing revealed that, in these mice, whisker patterns develop in the trigeminal brainstem but do not develop in the somatosensory thalamus. Subsequently, there is no barrel formation in the neocortex yet a partial afferent patterning develops. Whisker stimulation evokes weak cortical activity and presynaptic neurotransmitter release probability is also affected. We found several behavioral deficits in tasks, ranging from sensorimotor to social and cognitive. Collectively, these results show that thalamic NMDARs play a critical role in the patterning of the somatosensory thalamic and cortical maps and their impairment may lead to pronounced behavioral defects.

Role of whiskers in sensorimotor development of C57BL/6 mice

“…16,22,23]. In the present study, whisker trimming in mouse pups from P3 onwards led to reduce body weight gain by P17.…”

“…Pups were housed with their dams but they needed to search and find solid food by themselves as the onset of self-feeding. Whisker clipped mice clearly showed a decreased investigation in the open arena and toward placed objects and significant impairment in texture/shape recognition [22,63]. It is highly possible that the deafferentation of whiskers induces delayed transition to solid food or impairment in solid food feeding.…”

“…The frequencies and the types of whisking toward the objects or in open air were quantified, by counting whisker movement in each frame of the video recordings for at least 3 sec length for each whisker motion. The total duration of each video recorded was minimum 4 minute [e.g., 22]. …”

“…The stimulus dependent, rhythmic patterns of whisker movement allows them detailed shape/texture analysis [9,18,21]. A lack of function in whisker-derived somatosensory neural pathway induces several impairment in tactile and motor coordinative behaviors [22,23]. Thus, whisking leads to sensorimotor activity that eventually guides adaptive behaviors.…”

Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer's disease

“…The Ymaze test was performed for a short-term, working memory task as described (Arakawa et al, 2014; Bryan et al, 2010) utilizing a Y-shaped maze with an arm length of 35 cm, width of 6 cm, and height of 10 cm. Each mouse was tested for 5–14 min until the animal made 20 arms choices.…”