Mapping the physiological and molecular markers of stress and SSRI antidepressant treatment in S100a10 corticostriatal neurons.

In mood disorders, psychomotor and sensory abnormalities are prevalent, disabling, and intertwined with emotional and cognitive symptoms. Corticostriatal neurons in motor and somatosensory cortex are implicated in these symptoms, yet mechanisms of their vulnerability are unknown. Here, we demonstrate that S100a10 corticostriatal neurons exhibit distinct serotonin responses and have increased excitability, compared with S100a10-negative neurons. We reveal that prolonged social isolation disrupts the specific serotonin response which gets restored by chronic antidepressant treatment. We identify cell-type-specific transcriptional signatures in S100a10 neurons that contribute to serotonin responses and strongly associate with psychomotor and somatosensory function. Our studies provide a strong framework to understand the pathogenesis and create new avenues for the treatment of mood disorders.

Distribution of c-Fos immunoreactivity in the rat brain following abuse-like toluene vapor inhalation.

Inhalation of vapors from toluene-containing products results in euphoria accompanied by a variety of cognitive impairments and motor dysfunctions. The profound behavioral changes observed during and following toluene inhalation suggest changes in the activity of cells in potentially many brain regions; however, a comprehensive assessment of the neuroanatomical structures activated by toluene vapor has not been completed. Thus in the present study we systematically mapped in over 140 brain structures the distribution of c-Fos immunoreactivity (c-Fos IR), a proxy for neural activation, following exposure to an abuse-like concentration (~5000 ppm) of toluene vapor for 0, 5, 10 or 30 min. Quantitative analyses revealed increases in c-Fos IR in about one-third of the brain structures examined, with most of these structures significantly activated only after prolonged toluene exposure. The majority of brain structures activated by toluene were found in the forebrain and midbrain, with particularly pronounced activation in nuclei implicated in the processing of rewarding, emotional, and olfactory stimuli, and those controlling motor output. These structures included the ventral tegmental area, nucleus accumbens, select regions of the amygdala and hypothalamus, cingulate cortex, olfactory nuclei, piriform cortex, secondary motor cortex and caudate-putamen. In contrast, all subregions of the hippocampus and most thalamic nuclei were not significantly activated by toluene vapor. In the brainstem, effects of toluene vapor were restricted to select nuclei in the pons. The pattern of c-Fos IR evoked by inhalation of toluene vapor appears distinct from other psychoactive substances, consistent with the unique and complex behavioral outcomes associated with acute toluene inhalation.