Activity of Neurons in the Basal Magnocellular Nucleus During Performance of an Operant Task

Spike activity was studied in 95 neurons in the basal magnocellular nucleus in rabbits during spontaneous behavior and during performance of a conditioned operant response. Nearly half the neurons (48.4%) showed significant (p < 0.05) negative correlations between spontaneous discharges and the power of the frontal lobe EEG delta rhythm; most of these cells could be identified as cholinergic projection neurons. Neurons of this group had predominantly excitatory responses to the conditioned stimulus during performance of the operant task, while the responses to the conditioned stimulus of presumptively non-cholinergic neurons, not projecting to the cortex, were mainly inhibitory. The activatory responses of neurons in the basal magnocellular nucleus to the conditioned stimulus were markedly stronger while the animals performed the operant response as compared with performances in which there was no response to the conditioned stimulus. These results provide evidence that the basal magnocellular nucleus supports the level of waking and attending required for performance of operant conditioned reflex activity.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.