Identification of novel spinal cholinergic genetic subtypes disclose Chodl and Pitx2 as markers for fast motor neurons and partition cells

Abstract

Spinal cholinergic neurons are critical for motor function in both the autonomic and somatic nervous systems and are affected in spinal cord injury and in diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. Using two screening approaches and in situ hybridization, we identified 159 genes expressed in typical cholinergic patterns in the spinal cord. These include two general cholinergic neuron markers, one gene exclusively expressed in motor neurons, and nine genes expressed in unknown subtypes of somatic motor neurons. Further, we present evidence that chondrolectin (Chodl) is expressed by fast motor neurons and that estrogen-related receptor beta (ERRbeta) is a candidate marker for slow motor neurons. In addition, we suggest paired-like homeodomain transcription factor 2 (Pitx2) as a marker for cholinergic partition cells.

Potassium currents dynamically set the recruitment and firing properties of F-type motoneurons in neonatal mice

“…Finally, the immediate-firing motoneurons express ERR␤ but do not express chondrolectin. This was suggested to be the molecular signature of S-type motoneurons (Enjin et al 2010). In sharp contrast, none of the delayed-firing motoneurons expresses ERR␤, suggesting that they are F-type motoneurons, and the largest ones, i.e., those with the largest rheobase, do express chondrolectin.…”

Neuronal subtype specification in the spinal cord of a protovertebrate

“…Recently, Pitx2 was identified as a novel marker of cholinergic spinal interneurons in mouse (Enjin et al, 2010). A11.117 is also cholinergic and its lack of endplates further suggests a cholinergic interneuron identity.…”

Developmental Disruption of Recurrent Inhibitory Feedback Results in Compensatory Adaptation in the Renshaw Cell–Motor Neuron Circuit

“…In recent years, suggestions for the role of Renshaw cells have covered their involvement in speed and force regulation (Kiehn, 2006;Alvarez and Fyffe, 2007) through to sculpting the spiking activity of motor neurons (Pratt and Jordan, 1987;Brownstone and Bui, 2010). Our results support a role for Renshaw cells in modifying motor neuron activity but, in the absence of a locomotor phenotype, do not support a direct role in speed or force regulation.…”

“…The Viaat (SLC32A1) cRNA probe covered nucleotides 588 -2072 (GeneID: 22348/NM_009508.2). The following antibodies were used in the immunohistochemistry procedures: polyclonal goat anti-ChAT (1:100; AB144P, Millipore); polyclonal goat anti-vesicular acetylcholine transporter (VAChT; 1:500; AB1578, Millipore); polyclonal rabbit and guinea pig anti-vesicular glutamate transporter 1 (VGluT; both at 1:300; Fujiyama et al, 2001); polyclonal rabbit anti-calbindin (1:5000; CB38, Swant); monoclonal mouse anti-VIAAT (1:500; 131 011, Synaptic Systems); and monoclonal mouse anti synaptophysin (1:500; Sigma-Aldrich). Images were captured on a Zeiss LSM Meta 510 confocal microscope and analyzed using ImageJ software.…”