Regional difference in spontaneous firing inhibition by GABA(A) and GABA(B) receptors in nigral dopamine neurons

GABAergic control over dopamine (DA) neurons in the substantia nigra is crucial for determining firing rates and patterns. Although GABA activates both GABA(A) and GABA(B) receptors distributed throughout the somatodendritic tree, it is currently unclear how regional GABA receptors in the soma and dendritic compartments regulate spontaneous firing. Therefore, the objective of this study was to determine actions of regional GABA receptors on spontaneous firing in acutely dissociated DA neurons from the rat using patch-clamp and local GABA-uncaging techniques. Agonists and antagonists experiments showed that activation of either GABA(A) receptors or GABA(B) receptors in DA neurons is enough to completely abolish spontaneous firing. Local GABA-uncaging along the somatodendritic tree revealed that activation of regional GABA receptors limited within the soma, proximal, or distal dendritic region, can completely suppress spontaneous firing. However, activation of either GABA(A) or GABA(B) receptor equally suppressed spontaneous firing in the soma, whereas GABA(B) receptor inhibited spontaneous firing more strongly than GABA(A) receptor in the proximal and distal dendrites. These regional differences of GABA signals between the soma and dendritic compartments could contribute to our understanding of many diverse and complex actions of GABA in midbrain DA neurons.

FGF8 is Essential for Functionality of Induced Neural Precursor Cell-derived Dopaminergic Neurons

Induced neural precursor cells (iNPCs) are one source of transplantable dopaminergic neurons used in cell therapy for Parkinson's disease. In the present study, we demonstrate that iNPCs can be generated by transducing Brn2, Ascl1, Myt1L and Bcl-xL in a culture supplemented with several mitogens and subsequently can be differentiated to dopaminergic neurons (DA). However, studies have shown that iDA and/or iNPC-derived DA neurons using various conversion protocols have low efficiency. Here, we show that early exposure of FGF8 to fibroblasts efficiently improves differentiation of DA neurons. So our study demonstrates that FGF8 is a critical factor for generation of iNPC-derived DA neurons.