Loss of afferent input alters voltage gated ion channel and neuromodulator receptor expression in crustacean and mammalian neurons

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Neural networks need to generate appropriate output regardless of external stimuli, to ensure survival of the organism. We utilize the crustacean stomatogastric ganglion (STG) and the mouse major pelvic ganglion (MPG) to investigate why perturbations to such networks induce homeostatic compensation, and how this affects the network's ability to generate appropriate output. We assessed whether changes in expression of select transcripts constitute homeostatic compensation for loss of afferent input or disease. We use the STG as proof of concept to investigate impacts of loss of neuromodulation and subsequent compensatory responses, then utilize the MPG to implicate these kinds of responses as general characteristics across nervous systems. The STG is dependent on neuromodulation from anterior ganglia for proper output. Previous studies showed that deafferentation of the pyloric network attenuates output. We investigated whether reconnected input to the STG restored normal pyloric output. We found that the deafferented pyloric pacemaker responds differentially to restored inputs as well as exogenously applied neurotransmitters. Normal bladder function requires coordination of the central and peripheral nervous system. Peripheral nerve injury can be caused by surgery in the pelvic region or spinal cord injury. The main sequela is loss of bladder control. We will investigate if injury or disease alter gene expression patterns in MPG neurons. Using quantitative PCR on whole MPG, we observed changes in a select group of channel and receptor genes. These data demonstrate that perturbations to neural networks that alter their neuromodulatory input cause them undergo changes in transcription and functional output.