Biomedical subjects
Publications and source records attributed to E P Huang.
Synaptic activity can induce neurons to synthesize proteins important for cognition and brain development. Recent results suggest this activity-induced protein synthesis is partially mediated by regulated translation within neuronal dendrites.
Recent studies suggest that transmitter molecules released at central synapses sometimes diffuse long enough distances to activate receptors located outside the synaptic cleft or even in neighboring synapses. This transmitter 'spillover' may have important physiological consequences.
Early and late expressing components of synaptic plasticity may underlie the temporal phases of behavioral memory. New studies argue that a balance between kinase and phosphatase activity regulates the transition between different phases of synaptic plasticity and memory.
A widely accepted hypothesis suggests that changes in synaptic strength underlie the formation of memories in the brain. LTP is a mechanism of synaptic strengthening. Induction of LTP depends on NMDA receptor activation, and its expression depends in part on protein kinase activity. Studies of knock-out mice suggest that LTP is critical for hippocampus-based memory. Genetic studies in Drosophila implicate cAMP metabolism in classical conditioning, a form of unconscious memory. Consolidating memories for long-term retention depends on the cAMP-inducible transcription factor CREB.
Hippocampal pyramidal neurons often fire in bursts of action potentials with short interspike intervals (2-10 msec). These high-frequency bursts may play a critical role in the functional behavior of hippocampal neurons, but synaptic plasticity at such short times has not been carefully studied. To study synaptic modulation at very short time intervals, we applied pairs of stimuli with interpulse intervals ranging from 7 to 50 msec to CA1 synapses isolated by the method of minimal stimulation in hippocampal slices. We have identified three components of short-term paired-pulse modulation, including (i) a form of synaptic depression manifested after a prior exocytotic event, (ii) a form of synaptic depression that does not depend on a prior exocytotic event and that we postulate is based on inactivation of presynaptic N-type Ca2+ channels, and (iii) a dependence of paired-pulse facilitation on the exocytotic history of the synapse.
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Nitric oxide is back in the spotlight with a new series of studies showing that it plays an important role in long-term potentiation, the best-studied type of synaptic plasticity in the central nervous system thought likely to play an important role in learning and memory.
Using whole cell recording from CA1 hippocampal pyramidal neurons in slices, we examined the progressive decrease of N-methyl-D-aspartate receptor-mediated synaptic responses in the presence of the open-channel blocker MK-801. Previous studies analyzing this decrease have proposed that hippocampal synapses fall into two distinct classes of release probabilities, whereas studies based on other methods indicate a broad distribution of synaptic reliabilities exists. Here we derive the theoretical relationship between the MK-801-mediated decrease in excitatory postsynaptic current amplitudes and the underlying distribution of synaptic reliabilities. We find that the MK-801 data are consistent with a continuous distribution of synaptic reliabilities, in agreement with studies examining individual synapses. In addition, changes in the MK-801-mediated decrease in response size as a consequence of altering release probability are consistent with this continuous distribution of synaptic reliabilities.
It has been argued by Watson, Barlow and Robson that the visual stimulus that humans detect best specifies the spatial-temporal structure of the receptive field of the most sensitive visual neurons. To investigate 'what the eye sees best' they used stimuli that varied in luminance alone. Because the most abundant primate retinal ganglion cells, the P cells, are colour-opponent, we might expect that a coloured pattern would also be detected well. We generalized Watson et al.'s study to include variations in colour as well as luminance. We report here that our best detected coloured stimulus was seen 5-9-fold better than our best luminance spot and 3-8-fold better than Watson's best luminance stimulus. The high sensitivity to colour is consistent with the prevalence and high colour contrast-gain of retinal P cells, and may compensate for the low chromatic contrasts typically found in natural scenes.
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