Parkinson disease is a common neurodegenerative disorder that leads to difficulty in effectively translating thought into action. Although it is known that dopaminergic neurons that innervate the striatum die in Parkinson disease, it is not clear how this loss leads to symptoms. Recent work has implicated striatopallidal medium spiny neurons (MSNs) in this process, but how and precisely why these neurons change is not clear. Using multiphoton imaging, we show that dopamine depletion leads to a rapid and profound loss of spines and glutamatergic synapses on striatopallidal MSNs but not on neighboring striatonigral MSNs. This loss of connectivity is triggered by a new mechanism-dysregulation of intraspine Cav1.3 L-type Ca(2+) channels. The disconnection of striatopallidal neurons from motor command structures is likely to be a key step in the emergence of pathological activity that is responsible for symptoms in Parkinson disease.

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Expression from a short human cytomegalovirus (HCMV) major immediate early (IE) promoterenhancer was tested in three different virus vectors : recombinant adenovirus (Ad), recombinant herpes simplex virus type 1 (HSV-1) and HSV-1-derived amplicon vectors. The HCMV major IE promoterenhancer within a replication-deficient recombinant Ad vector was shown to produce cell-specific expression in rat nervous system cell cultures. Recombinant Ad entered all cell types examined but the HCMV major IE promoter was silent in primary cultures of neocortical neurons and Schwann cells, although it drove transgene expression in astrocytes and fibroblasts. Moreover, in neurons and Schwann cells, expression from the HCMV major IE

Somatic cell reprogramming holds great promise for the development of novel cellular therapeutics. A number of sources of reprogramming potential have been identified, including oocytes, embryonic germ (EG) cells and embryonic stem (ES) cells. However, each of these sources of reprogramming factors is problematic, since they are either not freely available or have special growth requirements. Embryonal carcinoma (EC) cells are another source of pluripotent cells that, unlike ES and EG cells, do not usually require special growth conditions. Since they share many of the key characteristics of ES cells, such as pluripotency, EC cells may provide a readily amenable alternative source of reprogramming factors and could serve as a model for ES cells in this respect. Here we show that mouse EC cells can also function as donors of reprogramming factors. PEG-mediated fusion between murine EC cells (P19) and the cells of a human T-lymphoma cell line (CEM-GFP) resulted in inter-species hybrid colony formation. Colonies of hybrid cells displayed heterogeneity in cellular morphology as well as in their pattern of human gene expression. Expression of two human transcription factors characteristic of undifferentiated pluripotent stem cells, Oct-4 and Sox-2, was detected in the hybrid cells, demonstrating activation of endogenous human markers of pluripotency. Simultaneously, down-regulation of CD45, a marker present in lymphocytic cells, was observed in some hybrids. The detection of human specific markers of differentiation, such as nestin, lamininbeta1, and collagen IValpha1, indicates that fusion resulted in reprogramming of the human cells to reflect the differentiation potential of the murine EC partner.

The existence of direct synaptic input from the neocortex to intermediate zone and white matter interstitial neurons was examined in both neonate and adult cats. This projection was studied by injecting the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the neocortex and examining whether cortical efferent axons formed synapses in the intermediate zone or white matter. Anterogradely labeled boutons establishing synapses in the intermediate zone and white matter were found at the electron microscopic level after injecting PHA-L into the primary visual, somatosensory, and suprasylvian cortex. Although labeled synapses were found in the intermediate zone of kittens injected at postnatal days 2 and 6, their morphological features appeared immature compared to those found in kittens aged 3 weeks or in adults. Postsynaptic targets of efferent cortical axons were studied in serial sections and shown to be dendritic shafts and spines. This paper shows that cortical efferent axons contribute synapses to interstitial neurons located in the intermediate zone of kittens and white matter of adults. The functional role of the corticointermediate zone/white matter projection remains to be determined.