Search PubMed⌕ Search

Biomedical subjects

Hugh P C Robinson

Publications and source records attributed to Hugh P C Robinson.

9 recordsLinked to original sources

Coding with spike shapes and graded potentials in cortical networks.

In cortical neurones, analogue dendritic potentials are thought to be encoded into patterns of digital spikes. According to this view, neuronal codes and computations are based on the temporal patterns of spikes: spike times, bursts or spike rates. Recently, we proposed an 'action potential waveform code' for cortical pyramidal neurones in which the spike shape carries information. Broader somatic action potentials are reliably produced in response to higher conductance input, allowing for four times more information transfer than spike times alone. This information is preserved during synaptic integration in a single neurone, as back-propagating action potentials of diverse shapes differentially shunt incoming postsynaptic potentials and so participate in the next round of spike generation. An open question has been whether the information in action potential waveforms can also survive axonal conduction and directly influence synaptic transmission to neighbouring neurones. Several new findings have now brought new light to this subject, showing cortical information processing that transcends the classical models.

Action Potentials↗

Correlation entropy of synaptic input-output dynamics.

The responses of synapses in the neocortex show highly stochastic and nonlinear behavior. The microscopic dynamics underlying this behavior, and its computational consequences during natural patterns of synaptic input, are not explained by conventional macroscopic models of deterministic ensemble mean dynamics. Here, we introduce the correlation entropy of the synaptic input-output map as a measure of synaptic reliability which explicitly includes the microscopic dynamics. Applying this to experimental data, we find that cortical synapses show a low-dimensional chaos driven by the natural input pattern.

Action Potentials↗

Electrophysiological and gene expression profiling of neuronal cell types in mammalian neocortex.

It is a challenging question to understand how different neuronal types are organized into a complex architecture in the cortex, an architecture which is also adapted in different regions to subserve very different functions. Recent developments in genetic and molecular techniques have opened up the possibility of using gene expression profiling for neuronal cell typing, with the aim of uncovering novel cell types and the underlying mechanisms which generate and maintain neuronal heterogeneity in the cortex. This review introduces some current ideas about neuronal cell types in the cortex and describes recent approaches to expression profiling for defining cortical neuronal cell types.

Animals↗

Stimulus history reliably shapes action potential waveforms of cortical neurons.

Action potentials have been shown to shunt synaptic charge to a degree that depends on their waveform. In this way, they participate in synaptic integration, and thus in the probability of generating succeeding action potentials, in a shape-dependent way. Here we test whether the different action potential waveforms produced during dynamical stimulation in a single cortical neuron carry information about the conductance stimulus history. When pyramidal neurons in rat visual cortex were driven by a conductance stimulus that resembles natural synaptic input, somatic action potential waveforms showed a large variability that reliably signaled the history of the input for up to 50 ms before the spike. The correlation between stimulus history and action potential waveforms had low noise, resulting in information rates that were three to four times larger than for the instantaneous spike rate. The reliable correlation between stimulus history and spike waveforms then acts as a local encoding at the single-cell level. It also directly affects neuronal communication as different waveforms influence the production of succeeding spikes via differential shunting of synaptic charge. Modeling was used to show that slow conductances can implement memory of the stimulus history in cortical neurons, encoding this information in the spike shape.

Action Potentials↗

Statistics of decision making in the leech.

Animals continuously decide among different behaviors, but, even in invertebrates, the mechanisms underlying choice and decision are unknown. In this article, leech spontaneous behavior was tracked and quantified for up to 12 h. We obtained a statistical characterization, in space and time domains, of the decision processes underlying selection of behavior in the leech. We found that the spatial distribution of leech position in a uniform environment is isotropic (the same in all directions), but this isotropy is broken in the presence of localized external stimuli. In the time domain, transitions among behaviors can be described by a Markov process, the structure of which (allowed states and transitions) is highly conserved across individuals. Finally, a wide range of recurrent, deterministic motifs was identified in the apparently irregular and unstructured exploratory behavior. These results provide a rigorous description of the inner dynamics that control the spontaneous and continuous flow of behavioral decisions in the leech.

Animals↗

Fast and slow voltage-dependent dynamics of magnesium block in the NMDA receptor: the asymmetric trapping block model.

The NMDA receptor (NMDAR) produces a long-lasting component of the glutamatergic EPSC in mammalian central neurons. The current through NMDARs is voltage dependent as a result of block by extracellular magnesium, which has recently been shown to give rise to a complex time dependence, with fast and slow components of responses to changes in membrane potential. Here, we studied the dynamics of block and unblock by measuring voltage step responses in conjunction with fast perfusion of agonist in nucleated patches isolated from rat cortical pyramidal neurons. We found that slow unblock shows a progressive onset during synaptic-like responses to brief pulses of agonist. Repolarizing briefly from +40 to -70 mV revealed that slow unblock is reestablished with a time constant of approximately 5 msec at room temperature. Also, the time course of deactivation, in response to a pulse of agonist, slows twofold over the potential range -30 to +40 mV. An asymmetric "trapping block" model in which the voltage-independent closing rate constant of the blocked channel is approximately three times that of the unblocked channel accounts quantitatively for all of these phenomena and for responses to action potential waveform clamp. This model allows much more accurate prediction of NMDAR current in physiological conditions of magnesium concentration and changing membrane potential than previously possible. It suggests a positive allosteric link between occupation of the NMDAR pore by magnesium and closure of the permeation gate.

Animals↗

A slow fraction of Mg2+ unblock of NMDA receptors limits their contribution to spike generation in cortical pyramidal neurons.

The timing of voltage-dependent removal of Mg(2+) block of N-methyl-d-aspartate receptors (NMDARs) is potentially critical for determining their nonlinear contribution to excitability. Here, we measure the kinetics of NMDAR unblock in nucleated patch and whole cell recordings of rat cortical pyramidal neurons during depolarizing voltage steps. At room temperature, the unblock showed a very fast component (tau < 1 ms) and a slower component (tau = 14-23 ms in nucleated patches). The slow component accounted for half of the current at +40 mV and its amplitude and time constant showed some voltage dependence. Blocking with hyperpolarization was very fast (tau < 200 micros). Voltage-clamp with action potential waveforms, at both room temperature and at 33 degrees C, showed that the rising phase of single fast action potentials unblocks far less NMDAR current than expected from the stationary voltage dependence, while a large amplitude of current is uncovered during the upstroke of slow calcium action potentials. The repolarization of fast sodium action potentials uncovers an NMDAR tail current, much bigger than the stationary level of current.

Action Potentials↗

A system for MEA-based multisite stimulation.

The capability for multisite stimulation is one of the biggest potential advantages of microelectrode arrays (MEAs). There remain, however, several technical problems which have hindered the development of a practical stimulation system. An important design goal is to allow programmable multisite stimulation, which produces minimal interference with simultaneous extracellular and patch or whole cell clamp recording. Here, we describe a multisite stimulation and recording system with novel interface circuit modules, in which preamplifiers and transistor transistor logic-driven solid-state switching devices are integrated. This integration permits PC-controlled remote switching of each substrate electrode. This allows not only flexible selection of stimulation sites, but also rapid switching of the selected sites between stimulation and recording, within 1.2 ms. This allowed almost continuous monitoring of extracellular signals at all the substrate-embedded electrodes, including those used for stimulation. In addition, the vibration-free solid-state switching made it possible to record whole-cell synaptic currents in one neuron, evoked from multiple sites in the network. We have used this system to visualize spatial propagation patterns of evoked responses in cultured networks of cortical neurons. This MEA-based stimulation system is a useful tool for studying neuronal signal processing in biological neuronal networks, as well as the process of synaptic integration within single neurons.

Action Potentials↗

Stages of spike time variability during neuronal responses to transient inputs.

In cerebral cortex, cells tend to fire in response to strong transient fluctuations in input, produced by synchronous population activity, which reset the precision of firing and erase correlations between prior and future spike times. Here, using experiments and modeling, we study the accumulation of spike time variance in response to single decaying transient stimuli. All such responses go through distinct stages in time. When the stimulus is high, variance is held low, while at low stimulus levels near threshold, variance rises dramatically, approaching a Poisson level. This behavior was reproduced in a stochastically simulated Hodgkin-Huxley model, and in two simpler models, class 1 (Morris-Lecar) and class 2 (FitzHugh-Nagumo), incorporating Ornstein-Uhlenbeck noise. Early stage variance represents perturbation of uniform limit-cycle motion of the dynamical variables. Late stage variance reflects random motion of the dynamical variables captured within the basin of the resting fixed point. We show that the two stages have different sensitivities to the amplitude and time scale of noise, and relate this to coherence resonance. This rapid breakdown in reliability during responses to transient stimuli may restrict precise signalling by spike times to brief time windows, and limit the duration of coherent synchronous responses in the cortex.

Action Potentials↗