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The transcription factor CREB is involved in mediating many of the long-term effects of activity-dependent plasticity at glutamatergic synapses. Here, we show that activation of NMDA receptors and voltage-sensitive calcium channels leads to CREB-mediated transcription in cortical neurons via a mechanism regulated by CREB-binding protein (CBP). Recruitment of CBP to the promoter is not sufficient for...
The glutamatergic neuromuscular junction (NMJ) in Drosophila adds new boutons and branches during larval development. We generated transgenic fruit flies that express a novel green fluorescent membrane protein at the postsynaptic specialization, allowing for repeated noninvasive confocal imaging of synapses in live, developing larvae. As synapses grow, existing synaptic boutons stretch apart and new...
We have investigated the specification of noradrenergic neurotransmitter identity in neural crest stem cells (NCSCs). Retroviral expression of both wild-type and dominant-negative forms of the paired homeodomain transcription factor Phox2a indicates a crucial and direct role for this protein (and/or the closely related Phox2b) in the regulation of endogenous tyrosine hydroxylase (TH) and dopamine-β...
This study of rat cerebellar slices yielded two lines of evidence indicating that the corticotropin-releasing factor (CRF) found in climbing fibers (CFs) is critical for the induction of long-term depression (LTD) at the parallel fiber (PF) synapses of Purkinje cells (PCs) by their conjunctive activation with either stimulation of CFs or depolarization of PCs. First, LTD induction was effectively...
We have studied the effect of unilateral autografts of carotid body cell aggregates into the putamen of MPTP-treated monkeys with chronic parkinsonism. Two to four weeks after transplantation, the monkeys initiated a progressive recovery of mobility with reduction of tremor and bradykinesia and restoration of fine motor abilities on the contralateral side. Apomorphine injections induced rotations...
Little is known about how the generation of specific neuronal types at stereotypic positions within the hindbrain is linked to Hox gene–mediated patterning. Here, we show that during neurogenesis, Hox paralog group 2 genes control both anteroposterior (A-P) and dorsoventral (D-V) patterning. Hoxa2 and Hoxb2 differentially regulate, in a rhombomere-specific manner, the expression of several genes in...
In the α7 nicotinic acetylcholine receptors, we analyze the contribution of mutations E237A and V251T, together with the proline insertion P236′, in the conversion of the charge selectivity from cationic to anionic. We show that the triple mutant exhibits spontaneous openings displaying anionic selectivity. Furthermore, at position 251, hydrophilic or even negatively charged residues are compatible...
Different Drosophila photoreceptors (R cells) connect to neurons in different optic lobe layers. R1–R6 axons project to the lamina; R7 and R8 axons project to separate layers of the medulla. We show a receptor tyrosine phosphatase, PTP69D, is required for lamina target specificity. In Ptp69D mutants, R1–R6 project through the lamina, terminating in the medulla. Genetic mosaics, transgene rescue, and...
Group I mGluRs heterologously expressed in sympathetic neurons inhibited calcium (I Ca ) and M-type potassium (I M ) currents. Treatment with pertussis toxin (PTX) revealed a voltage-dependent (VD), PTX-sensitive component of I Ca inhibition and a voltage-independent (VI), PTX-insensitive component. Coexpression of RGS2 occluded mGluR1a inhibition of I M and made I...
Slob is a novel protein that binds to the carboxy-terminal domain of the Drosophila Slowpoke (dSlo) calcium-dependent potassium (K Ca ) channel. A yeast two-hybrid screen with Slob as bait identifies the ζ isoform of 14–3–3 as a Slob-binding protein. Coimmunoprecipitation experiments from Drosophila heads and transfected cells confirm that 14–3–3 interacts with dSlo via Slob. All three proteins...
We report the role of dCREB2, the Drosophila homolog of CREB/CREM, in circadian rhythms. dCREB2 activity cycles with a 24 hr rhythm in flies, both in a light:dark cycle and in constant darkness. A mutation in dCREB2 shortens circadian locomotor rhythm in flies and dampens the oscillation of period, a known clock gene. Cycling dCREB2 activity is abolished in a period mutant, indicating that dCREB2...
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