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Jonathan B Demb

Publications and source records attributed to Jonathan B Demb.

8 recordsLinked to original sources
PubMed2006

Presynaptic mechanism for slow contrast adaptation in mammalian retinal ganglion cells.

Visual neurons, from retina to cortex, adapt slowly to stimulus contrast. Following a switch from high to low contrast, a neuron rapidly decreases its responsiveness and recovers over 5-20 s. Cortical adaptation arises from an intrinsic cellular mechanism: a sodium-dependent potassium conductance that causes prolonged hyperpolarization. Spiking can drive this mechanism, raising the possibility that the same mechanism exists in retinal ganglion cells. We found that adaptation in ganglion cells corresponds to a slowly recovering afterhyperpolarization (AHP), but, unlike in cortical cells, this AHP is not primarily driven by an intrinsic cellular property: spiking was not sufficient to generate adaptation. Adaptation was strongest following spatial stimuli tuned to presynaptic bipolar cells rather than the ganglion cell; it was driven by a reduced excitatory conductance, and it persisted while blocking GABA and glycine receptors, K((Ca)) channels, or mGluRs. Thus, slow adaptation arises from reduced glutamate release from presynaptic (nonspiking) bipolar cells.

Action Potentials↗
PubMed2005

Do we know what the early visual system does?

We can claim that we know what the visual system does once we can predict neural responses to arbitrary stimuli, including those seen in nature. In the early visual system, models based on one or more linear receptive fields hold promise to achieve this goal as long as the models include nonlinear mechanisms that control responsiveness, based on stimulus context and history, and take into account the nonlinearity of spike generation. These linear and nonlinear mechanisms might be the only essential determinants of the response, or alternatively, there may be additional fundamental determinants yet to be identified. Research is progressing with the goals of defining a single "standard model" for each stage of the visual pathway and testing the predictive power of these models on the responses to movies of natural scenes. These predictive models represent, at a given stage of the visual pathway, a compact description of visual computation. They would be an invaluable guide for understanding the underlying biophysical and anatomical mechanisms and relating neural responses to visual perception.

Animals↗
PubMed2005

Contrast adaptation in subthreshold and spiking responses of mammalian Y-type retinal ganglion cells.

Retinal ganglion cells adapt their responses to the amplitude of fluctuations around the mean light level, or the "contrast." But, in mammalian retina, it is not known whether adaptation arises exclusively at the level of synaptic inputs or whether there is also adaptation in the process of ganglion cell spike generation. Here, we made intracellular recordings from guinea pig Y-type ganglion cells and quantified changes in contrast sensitivity (gain) using a linear-nonlinear analysis. This analysis allowed us to measure adaptation in the presence of nonlinearities, such as the spike threshold, and to compare adaptation in subthreshold and spiking responses. At high contrast (0.30), relative to low contrast (0.10), gain reduced to 0.82 +/- 0.016 (mean +/- SEM) for the subthreshold response and to 0.61 +/- 0.011 for the spiking response. Thus, there was an apparent reduction in gain between the subthreshold and spiking response of 0.74 +/- 0.013. Control experiments suggested that the above effects could not be explained by an artifact of the intracellular recording conditions: extracellular recordings showed a gain change of 0.58 +/- 0.022. For intracellular recordings, negative current reduced the spike output but did not affect the gain change in the subthreshold response: 0.80 +/- 0.051. Thus, adaptation in the subthreshold response did not require spike-dependent conductances. We conclude that the contrast-dependent gain change in the spiking response can be explained by both a synaptic mechanism, as reflected by responses in the subthreshold potential, and an intrinsic mechanism in the ganglion cell related to spike generation.

Action Potentials↗
PubMed2004

How retinal ganglion cells prevent synaptic noise from reaching the spike output.

Synaptic vesicles are released stochastically, and therefore stimuli that increase a neuron's synaptic input might increase noise at its spike output. Indeed this appears true for neurons in primary visual cortex, where spike output variability increases with stimulus contrast. But in retinal ganglion cells, although intracellular recordings (with spikes blocked) showed that stronger stimuli increase membrane fluctuations, extracellular recordings showed that noise at the spike output is constant. Here we show that these seemingly paradoxical findings occur in the same cell and explain why. We made intracellular recordings from ganglion cells, in vitro, and presented periodic stimuli of various contrasts. For each stimulus cycle, we measured the response at the stimulus frequency (F1) for both membrane potential and spikes as well as the spike rate. The membrane and spike F1 response increased with contrast, but noise (SD) in the F1 responses and the spike rate was constant. We also measured membrane fluctuations (with spikes blocked) during the response depolarization and found that they did increase with contrast. However, increases in fluctuation amplitude were small relative to the depolarization (<10% at high contrast). A model based on estimated synaptic convergence, release rates, and membrane properties accounted for the relative magnitudes of fluctuations and depolarization. Furthermore, a cell's peak spike response preceded the peak depolarization, and therefore fluctuation amplitude peaked as the spike response declined. We conclude that two extremely general properties of a neuron, synaptic convergence and spike generation, combine to minimize the effects of membrane fluctuations on spiking.

Anesthetics, Local↗
PubMed2003

Different circuits for ON and OFF retinal ganglion cells cause different contrast sensitivities.

The theory of "parallel pathways" predicts that, except for a sign reversal, ON and OFF ganglion cells are driven by a similar presynaptic circuit. To test this hypothesis, we measured synaptic inputs to ON and OFF cells as reflected in the subthreshold membrane potential. We made intracellular recordings from brisk-transient (Y) cells in the in vitro guinea pig retina and show that ON and OFF cells in fact express significant asymmetries in their synaptic inputs. An ON cell receives relatively linear input that modulates a single excitatory conductance; whereas an OFF cell receives rectified input that modulates both inhibitory and excitatory conductances. The ON pathway, blocked by L-AP-4, tonically inhibits an OFF cell at mean luminance and phasically inhibits an OFF cell during a light increment. Our results suggest that basal glutamate release is high at ON but not OFF bipolar terminals, and inhibition between pathways is unidirectional: ON --> OFF. These circuit asymmetries explain asymmetric contrast sensitivity observed in spiking behavior.

Action Potentials↗
PubMed2002

Multiple mechanisms for contrast adaptation in the retina.

The retina adapts to average light intensity but also to the range of light intensities (contrast). A study by Baccus and Meister, in this issue of Neuron, identifies three ways that ganglion cells and interneurons adapt to high contrast: shorten integration time, reduce gain, and depolarize. Only the depolarization decays, over tens of seconds.

Action Potentials↗
PubMed2002

Connexin36 forms synapses essential for night vision.

Rod signals reach ganglion cells via at least five pathways. A new study in this issue of Neuron shows that all pathways from rods to ON-type ganglion cells require connexin36. This is the first physiological demonstration in mammals that a well-defined neural circuit requires a gap junction as an obligatory transmission step.

Animals↗