GABA-A receptors expression pattern in rat brain following low pressure distension of the stomach

It is known that gastric mechanoreceptor stimuli are widely integrated into neuronal circuits that involve visceral nuclei of hindbrain as well as several central brain areas. GABAergic neurons are widely represented in hindbrain nuclei controlling gastric motor functions, but limited information is available specifically about GABA(A)-responding neurons in brain visceral areas. The present investigation was designed to determine the central sensory neuronal pathways and their GABA(A)-alpha1 and -alpha3 receptor presenting neurons that respond to gastric mechanoreceptor stimulation within the entire rat brain. Low pressure gastric distension was used to deliver physiological mechanical stimuli in anesthetized rats, and different protocols of gastric distension were performed to mimic different stimulation patterns with and without sectioning vagal and/or splanchnic afferent nerves. Mapping of activated neurons was investigated using double colorimetric immunohistochemistry for GABA(A)-alpha1 or -alpha3 subunits and c-Fos. Following stomach distension, neurons expressing GABA(A) receptors with alpha1 or alpha3 subunits were detected. Low frequency gastric distension induced c-Fos expression in nucleus tractus solitarii (NTS) only, whereas in the high frequency gastric distension c-Fos positive nuclei were found in lateral reticular nucleus and in NTS in addition to some forebrain areas. In contrast, during the tonic-rapid gastric distension the neuronal activation was found in hindbrain, midbrain and forebrain areas. Moreover different protocols of gastric stimulation activated diverse patterns of neurons presenting GABA(A)-alpha1 or -alpha3 receptors within responding brain nuclei, which may indicate a probable functional significance of differential expression of GABA(A)-responding neurons. The same protocol of gastric distension performed in vagotomized rats has confirmed the primary role of the vagus in the response of activation of gastric brain areas, whereas neuronal input of splanchnic origins was shown to play an important role in modulating the mechanogastric response of brain areas.