Search

Protocadherin 9 (Pcdh9) is a member of the cadherin superfamily and is uniquely expressed in the vestibular and limbic systems; however, its physiological role remains unclear. Here, we studied the expression of Pcdh9 in the limbic system and phenotypes of Pcdh9-knock-out mice (Pcdh9 KO mice). Pcdh9 mRNA was expressed in the fear extinction neurons that express protein phosphatase 1 regulatory subunit 1 B (Ppp1r1b) in the posterior part of the basolateral amygdala (pBLA), as well as in the Cornu Ammonis (CA) and Dentate Gyrus (DG) neurons of the hippocampus. We show that the Pcdh9 protein was often localised at synapses. Phenotypic analysis of Pcdh9 KO mice revealed no apparent morphological abnormalities in the pBLA but a decrease in the spine number of CA neurons. Further, the Pcdh9 KO mice were related to features such as the abnormal optokinetic response, less approach to novel objects, and reduced fear extinction during recovery from the fear. These results suggest that Pcdh9 is involved in eliciting positive emotional behaviours, possibly via fear extinction neurons in the pBLA and/or synaptic activity in the hippocampal neurons, and normal optokinetic eye movement in brainstem optokinetic system-related neurons. [ABSTRACT FROM AUTHOR]

The pontine nuclei relay information derived from the cerebral cortex to the cerebellum. In addition to the motor command signals generated in the motor cortex, the cerebellum may generate motor command signals independent of the cerebral cortex using pontine nuclei-mediated signals. The cerebellar motor command signals generated in the vermis-medial cerebellar nuclear system may directly drive peripheral motoneurons in simple and autonomic movements. Those generated in the hemisphere-lateral cerebellar nuclear system, which are used in complicated movements, may not only drive the premotor or motor nuclei but may also be fed back to the cerebellum through the parvocellular red nucleus-inferior olive pathway, and may be compared with the motor command signals generated in the cerebral cortex. The long-term depression of parallel fiber-Purkinje cell synapses may be utilized in optimizing these cerebellar motor command signals. Voluntary movements may be executed through cooperation of the cerebellum- and cerebrum-generated motor command signals. [ABSTRACT FROM AUTHOR]

The afferent and efferent projections of the lobulus petrosus (LP) of the paraflocculus were examined by retrograde tracing with cholera toxin subunit B (CTB) and anterograde tracing with CTB or biotinylated dextran (BD) in the macaque. Following injections of the tracers into the LP, labeled neurons were seen mainly in the lateral, dorsal, paramedian and dorsolateral parts of the contralateral pontine nuclei (Pn) and in the ventromedial part of the principal olivary nucleus and the lateral pole of the medial accessory olivary nucleus at the rostral levels. Labeled terminals were seen ipsilaterally in the ventrolateral part of the posterior interposed nucleus and the basal interstitial nucleus of the cerebellum at their rostral levels, and in the ventromedial part of the lateral cerebellar nucleus. To reveal the connections between the LP-projecting pontine neurons and the corticopontine axons, BD was injected into the left prearcuate region or extrastriate visual areas, and CTB into the right LP. Labeled terminals from the prearcuate region were seen mainly in the left dorsal, medial and paramedian Pn, whereas those from the extrastriate visual areas were seen in the lateral and dorsolateral Pn. The distribution of the LP-projecting neurons overlapped that of the terminals from the extrastriate visual areas but did not overlap that of the terminals from the prearcuate region. The present study demonstrates that the LP of the monkey receives cortical visual inputs and projects to the posterior interposed and lateral cerebellar nuclei, suggesting that the LP may be involved in the control of voluntary eye movements. [ABSTRACT FROM AUTHOR]

Sources of mossy and climbing fiber inputs to the flocculus (FL), ventral paraflocculus (VP) and/or dorsal paraflocculus (DP) were identified in the vestibular ganglion, medulla oblongata and pons of 19 Wistar rats after 26 local injections of horseradish peroxidase, wheat-germ agglutinin-conjugated horseradish peroxidase, fast blue or diamidino yellow into the FL, VP and/or DP. There were large differences in the sources of mossy fibers to the FL and VP/DP. Labeled neurons after injections into the FL were observed mainly in the ipsilateral vestibular ganglion, bilaterally in the vestibular and prepositus hypoglossal nuclei, and in the caudal part of the nucleus reticularis tegmenti pontis. Labeled neurons were rarely observed in the pontine nuclei after localized injections into the FL. By contrast, after injections into the VP and/ or DP, numerous labeled neurons were observed in the pontine nuclei with a contralatetral predominance and in the rostral part of the nucleus reticularis tegmenti pontis bilaterally, but not in the vestibular nuclei in either side. Sources of climbing fibers to the FL and paraflocculus were completely contralateral to the injection side. After injection into the FL, labeled neurons were observed in the caudal dorsal cap and ventrolateral outgrowth of the inferior olivary nucleus. After injections into the VP, labeled neurons were observed mainly in the rostral dorsal cap, ventral medial accessory olivary nucleus (MAO) and caudal half of the ventral leaf of the principal olivary nucleus. After injections into the DP, labeled neurons were observed in the ventral MAO and caudal half of the ventral leaf of the principal olivary nucleus. These differences in the sources of mossy and climbing fiber inputs may suggest functional differences between the FL and VP/DP. The present results are consistent with our previous observations in monkey that the FL and VP/DP exhibit quite different mossy fiber input organizations. [ABSTRACT FROM AUTHOR]

Abstract: Ataxia and impaired motor learning are both fundamental features in diseases affecting the cerebellum. However, it remains unclarified whether motor learning is impaired only when ataxia clearly manifests, nor it is known whether the progression of ataxia, the speed of which often varies among patients with the same disease, can be monitored by examining motor learning. We evaluated motor learning and ataxia at intervals of several months in 40 patients with degenerative conditions [i.e., multiple system atrophy (MSA), Machado–Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3), SCA6, and SCA31]. Motor learning was quantified as the adaptability index (AI) in the prism adaptation task and ataxia was scored using the Scale for the Assessment and Rating of Ataxia (SARA). We found that AI decreased most markedly in both MSA-C and MSA-P, moderately in MJD, and mildly in SCA6 and SCA31. Overall, the AI decrease occurred more rapidly than the SARA score increase. Interestingly, AIs remained normal in purely parkinsonian MSA-P patients (n = 4), but they dropped into the ataxia range when these patients started to show ataxia. The decrease in AI during follow-up (dAI/dt) was significant in patients with SARA scores < 10.5 compared with patients with SARA scores ≥ 10.5, indicating that AI is particularly useful for diagnosing the earlier phase of cerebellar degeneration. We conclude that AI is a useful marker for progressions of cerebellar diseases, and that evaluating the motor learning of patients can be particularly valuable for detecting cerebellar impairment, which is often masked by parkinsonisms and other signs. [ABSTRACT FROM AUTHOR]