Within the cerebral and cerebellar cortices, neurons are organized in layers that segregate neurons with distinctive morphologies and axonal connections, and areas or regions that correspond to distinct functional domains. To explore the molecular underpinnings of pattern formation in layered regions of the CNS, we have characterized the patterns of expression of two homeodomain genes, Otx1 and...

In human and non-human primates, motor timing is considered to be dictated by cerebellar control of cortical activity, relayed through the cerebellar-thalamo-cortical (CTC) system. This supposition relies on studies that documented impairments in patients animal models. However, we know very little about way information integrated circuitry affect commands. We addressed this question probing CT...

Prenatal alcohol exposure is associated with microencephaly, cognitive and behavioral deficits, and growth retardation. Some of the mechanisms of ethanol-induced injury, such as high level oxidative stress and overexpression of pro-apoptotic genes, can increase the sensitivity of fetal neurons towards hypoxic/ischemic stress associated with normal labor. Thus, alcohol-induced sequelae may be th...

Unipolar brush cells (UBCs) are glutamatergic interneurons in the cerebellar cortex and dorsal cochlear nucleus. We studied the development of UBCs, using transcription factor Tbr2/Eomes as a marker for UBCs and their progenitors in embryonic and postnatal mouse cerebellum. Tbr2+ UBCs appeared to migrate out of the upper rhombic lip via two cellular streams: a dorsal pathway into developing cer...

Whether aggregates of prion protein (PrP) reflect neurotoxicity or are neuroprotective in prion diseases is unclear. To address this question, we performed a clinicopathologic study of cerebellar granular neurons in 100 patients affected with sporadic Creutzfeldt-Jakob disease (CJD). There was significant loss of these neurons in the subset of cases with Val/Val genotype at PRNP Codon 129 and M...

The brain's energy supply determines its information processing power, and generates functional imaging signals, which are often assumed to reflect principal neuron spiking. Using measured cellular properties, we analysed how energy expenditure relates to neural computation in the cerebellar cortex. Most energy is used on information processing by non-principal neurons: Purkinje cells use only ...

Progressive multifocal leukoencephalopathy (PML) remains an important complication of HIV-1/AIDS, despite widespread combined antiretroviral therapy (cART). As its name implies, it was long thought to be only a demyelinating disease restricted to brain white matter. However, JC virus (JCV), the causative agent of the classic PML form, infects glial cells and neurons, and is now known as the eti...

In a model of the cerebellar granular layer, pairs of neurons aligned along the parallel "ber axis "red synchronized over long distances provided the a!erent mossy "bers were spatially uniformly excited. Here, we applied a nonuniform mossy "ber input pattern and found that local patches of increased granule cell activity were sharpened by the feedback inhibition which granule cells received fro...

This schematic drawing shows the most relevant connections within a cerebellar module. The mossy fibers contact granule cells (GrC) and deep cerebellar nuclei (DCN) cells which, in turn, receive inhibition from the same common set of Purkinje cells (PC). Moreover, the interior olive (IO) cells emit climbing fibers that contact DCN cells and Purkinje cells (PC), which also project to the same DC...