December 7, 2020

Catalyst Research Project: Retrosplenial Cholinergic and Attentional-Motor Integration Dysfunction

PI: Omar Ahmed, PhD

Many PwP experience DRT-refractory spatial disorientation with inability to integrate external landmark cues with internal estimates of orientation.  The retrosplenial cortex (RSC) is critical for this function with fMRI studies indicating abnormal attentional information processing in PwP.  RSC, an integral AMI component, is densely interconnected with other AMI nodes, the cingulate cortex and anterior thalamus (locus of head position neurons), and receives dense BF cholinergic afferents.  These cholinergic inputs are critical for attentive spatial navigation. In work funded by a U-M Udall Center Pilot Project, Dr. Ahmed uncovered a unique pattern of local inhibition in the RSC. In this Catalyst Research Project, Dr. Ahmed will evaluate the hypotheses that thalamic input mediated spatial information is modulated by BF cholinergic afferents and that cholinergic receptor mediated responses in RSC neurons are critical for maintaining attentive navigation.  RSC inter-hemispheric communication is necessary to maintain attentive navigation.  Dr. Ahmed specifically hypotheses that cholinergic signaling is necessary for normal inter-hemispheric RSC function.  Dr. Ahmed will evaluate these hypotheses in both normal animals and in the dual lesion (DL) model of combined striatal dopaminergic denervation and cortical cholinergic denervation developed by Dr. Sarter.  This study will identify mechanisms of information transfer within a key AMI node. These experiments provide a cellular level examination of cholinergic functions within an AMI node, complementing the systems and circuit level approaches of the other projects.  The focus on attentive spatial navigation also complements Project I studies assessing the roles of deficient sensorimotor and visuomotor integration in PwP.