A Comprehensive Integrated Anatomical and Molecular Atlas of Rat Intrinsic Cardiac Nervous System.

We have developed and integrated several technologies including whole-organ imaging and software development to support an initial precise 3D neuroanatomical mapping and molecular phenotyping of the intracardiac nervous system (ICN). While qualitative and gross anatomical descriptions of the anatomy of the ICN have each been pursued, we here bring forth a comprehensive atlas of the entire rat ICN at single-cell resolution. Our work precisely integrates anatomical and molecular data in the 3D digitally reconstructed whole heart with resolution at the micron scale. We now display the full extent and the position of neuronal clusters on the base and posterior left atrium of the rat heart, and the distribution of molecular phenotypes that are defined along the base-to-apex axis, which had not been previously described. The development of these approaches needed for this work has produced method pipelines that provide the means for mapping other organs.

Ethanol and vestibular stimulation reveal simple and complex aspects of cerebellar heterogeneity.

Unlike the cerebral cortex, the cerebellum is characterized by a simple histological organization that is relatively uniform throughout. However, molecular characteristics of its constituent elements create a high degree of heterogeneity and complexity resulting in the delineation of modules defined by both parasagittal and anteroposterior boundaries. Eccles notion of the cerebellum as "designed to process input information in some unique and essential manner" may relate to analysis of temporal elements involved in both motor and cognitive behaviors. The complexity of molecular heterogeneities may provide for subtle alterations in temporal processing and lead to behavioral perturbations seen after alcohol or other disruptive stimuli.

Purkinje cell compartmentation of the cerebellum of microchiropteran bats.

Transverse boundaries divide the mammalian cerebellar cortex into transverse zones, and within each zone the cortex is further subdivided into a symmetrical array of parasagittal stripes. This topography is highly conserved across the Mammalia. Bats have a remarkable cerebellum with presumed adaptations to flight and to echolocation, but nothing is known of its compartmentation. We have therefore used two Purkinje cell compartmentation antigens, zebrin II/aldolase C and phospholipase Cbeta4, to reveal the topography of the cerebellum in microchiropteran bats. Three species of bat were studied, Lasiurus cinereus, Lasionycteris noctivagans, and Eptesicus fuscus. A reproducible pattern of zones and stripes was revealed that is similar across the three species. The architecture of the bat cerebellum conforms to the ground plan of other mammals. However, two exceptions to the highly conserved mammalian architectural plan were revealed. First, many Purkinje cells in lobule I express zebrin II. A zebrin II-immunopositive lobule I has not been seen previously in mammals but is characteristic of the avian cerebellum. Second, lobules VI-VII comprise the large central zone. Within the central zone two subdomains are evident, a small anterior subdomain (lobule VI) in which Purkinje cells are predominantly zebrin II-immunopositive/PLCbeta4-immunonegative, as in other mammals, and a posterior subdomain (lobule VII), in which alternating zebrin II/phospholipase Cbeta4 stripes are prominent.

Motion sickness may be caused by a neurohumoral action of acetylcholine.

The mechanism by which motion stimulation results in the autonomic responses, known as motion sickness, has remained somewhat of an enigma. Neural connections between the vestibular nuclei and the autonomic and emetic centers in the brainstem have been described, but these appear to be relatively sparse. Thus, new or additional mechanisms seem warranted to account for this curious relationship. A new hypothesis is herein presented which posits that acetylcholine (ACh) acts as a neurohumeral agent to bring about the symptoms associated with motion sickness. Motion stimulation will activate primary vestibular afferents leading to activation of secondary vestibulocerebellar fibers, some of which are cholinergic, projecting to the vestibulocerebellar region of the posterior cerebellum. The acetylcholine, once released from these synaptic terminals diffuses into the CSF in the 4th ventricle. From there it gains access to the autonomic and emetic centers within the dorsal brainstem and can activate the cholinergic receptors in these nuclei to produce the symptoms characteristic of motion sickness. In similar fashion ACh would have access to the vestibular nuclei where it will facilitate transmission in these nuclei further reinforcing the vestibulocerebellar activity. This would serve as a positive feedback loop which will result in additional release of ACh from the cerebellum and further activation of the brainstem nuclei that result in the symptoms of motion sickness.

The ventral uvula of the mouse cerebellum: a neural target of ethanol and vestibular stimuli.

The present study demonstrates that mice exposed to vertical translation stimulation exhibit a distinct parasagittal pattern of Fos-immunoreactive (Fos-IR) granule cells in the ventral uvula of the cerebellum. This pattern is identical to one produced by acute ethanol treatment. In contrast, yaw stimulation produces an entirely different pattern in this same region of the cerebellum. Similar results are obtained in the light or in total darkness. These results suggest an anatomical and functional organization within the granule cells of the ventral uvula that may be a common neural substrate for some effects of ethanol and particular vestibular stimuli.

An absence of tinnitus.

We present and discuss a case of lifelong tinnitus in an otolaryngologist (L.D.L.) followed by complete elimination of the tinnitus as a result of a cerebral vascular accident located in the left corona radiata. Pre- and post-CVA audiograms showed no change in hearing. A magnetic resonance imaging study of the brain documents the size and location of the lesion. Discussion looks at recent studies of the central nervous system showing evidence of increased activity related to tinnitus. Our assessment of the lesion and the resulting loss of tinnitus can be explained by the neurophysiological model of tinnitus, which includes plasticity of the central nervous system.

Acute ethanol administration produces specific patterns of localization of Fos-immunoreactivity in the cerebellum and inferior olive of two inbred strains of mice.

Genes play an important role in behavioral responses to ethanol. We examined the response of neurons within the inferior olivary complex (IO) and cerebellum of C57Bl6/J and C3H/HeJ mice to acute ethanol, using immunodetection of Fos (Fos-IR) protein as a marker of neuronal activation. The results demonstrate specific but different patterns of Fos-IR within the IO and cerebellum, especially lobule IX, in each strain. The Fos-IR banding pattern seen in the granule cells of lobule IX is aligned with a previously described banding pattern of Purkinje cells that constitutively expressed heat-shock protein-25 (HSP-25).

Alcohol differentially affects c-Fos expression in the supraoptic nucleus of long-sleep and short-sleep mice.

Ethanol administration in long-sleep (LS) and short-sleep (SS) mice results in a large number of Fos-IR neurons in the supraoptic nucleus (SON) in LS, and almost no Fos-IR neurons in the same nucleus in SS mice. In contrast, isotonic saline, hypertonic saline, with or without ethanol, resulted in a similar pattern of Fos-IR in both strains. These data indicate a differential effect of ethanol on c-Fos signaling specifically in the SON. Since the LS and SS mice were specifically selected for differential sensitivity to the sedative/hypnotic effects of ethanol, this differential in c-Fos activity may be causally implicated in their differential sensitivity to ethanol.