CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors

Striatal synaptic adaptations in Parkinson's disease

“…As this change in synaptic strength should be accompanied by a reduction in the size of spines, methods for spine counting that miss thin and stubby spines (which are abundant in SPNs ( Wilson et al, 1983 )) will lead to the conclusion that spines are lost, when they are not. For example, ( Gomez et al, 2019 ) used Lucifer Yellow fills to estimate spine density in SPNs, which resulted in an estimate of spined density in control SPNs that was roughly 50% of that measured with two-photon imaging of Alexa-filled SPNs ( Crittenden et al, 2021 ; Day et al, 2008 ; Fieblinger et al, 2014 ) or with a high voltage stereo electron microscopy ( Wilson et al, 1983 ). The mechanisms responsible for the relatively rapid loss of spines reported in dSPNs following intrastriatal 6-OHDA injections is less clear ( Suarez et al, 2016 ; Suarez et al, 2014 ).…”

Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients

“…Different lines of research, including single gene and GWAS, co-expression, and pathway analyses, along with pre-clinical studies converge on indicating RasGRP1 as a risk gene for SCZ [ 16 , 23 ]. Consistent with this evidence, RasGRP1 modulates dopamine signaling downstream of D1R activation via cAMP/PKA, mTOR/ERK pathways in the medium spiny neurons of caudate putamen [ 22 , 24 ], as well as regulates synaptic plasticity in the hippocampus [ 28 ]. Moreover, this protein also affects immune system processes [ 19 , 29 ] potentially implicated in pathophysiology of SCZ [ 30 ].…”

“…Total RNA was extracted from post-mortem tissues using RNeasy ® mini kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions [ 24 , 25 ]. Total RNA was purified to eliminate potentially contaminating genomic DNA using recombinant DNase (Qiagen, Hilden, Germany).…”

Emergence of rhythmic chunking in complex stepping of mice

“…Mice could run in dark conditions with the same proficiency as they did under light conditions. However, when their whiskers were trimmed, they were unable to run proficiently in the wheel (Crittenden et al ., 2021). These findings suggest that the differences in whisker sensibility could be involved in the individual differences in chunk locations.…”

“…The wheel turns at a constant speed under computer control, and water-restricted mice are required to run with complex stepping patterns without any specific instructions for the timing of each step in order to obtain reward. We have used this step-wheel task to examine sequential learning and performance of mice, including genetically modified mice (Crittenden et al, 2021; Kitsukawa et al, 2011; Nakamura et al, 2014, 2017, 2020). In this study, we found that as the training on complex steps progresses, the chunked sequences in which the movement parameters were stable became more pronounced and were gradually elongated, and that the motor coordination within the chunks was supported by the rhythm of these movements.…”