Neuronal adaptation in the somatosensory system of rodents.

The sensory systems in animals constantly monitor the environment and process salient and relevant features while subtracting background activity. This process requires continuous recalibration of neuronal gain based on recent history. Adaptation has been postulated to be the key mechanism by which neurons rapidly tune their response curves to represent the entire dynamic range of external inputs. Rodents heavily rely on their vibrissa system while gathering information about their surroundings using whisking. Neuronal adaptation is observed in all stages of sensory processing, from the whisker follicle through the brainstem and thalamus up to the barrel cortex. In this review, we discuss the intrinsic, synaptic and network mechanisms of adaptation such as short-term synaptic depression, inhibitory suppression, balance between excitation and inhibition as well as the role of cascading adaptation. Furthermore, we describe recent findings about the different intensity dependent adaptation properties in the two major somatosensory pathways and their possible implications about coding.

Dynamics of the orientation-tuned membrane potential response in cat primary visual cortex.

Neurons in the primary visual cortex are highly selective for stimulus orientation, whereas their thalamic inputs are not. Much controversy has been focused on the mechanism by which cortical orientation selectivity arises. Although an increasing amount of evidence supports a linear model in which orientation selectivity is conferred upon visual cortical cells by the alignment of the receptive fields of their thalamic inputs, the controversy has recently been rekindled with the suggestion that late cortical input--delayed by multiple synapses--could lead to sharpening of orientation selectivity over time. Here we used intracellular recordings in vivo to examine temporal properties of the orientation-selective response to flashed gratings. Bayesian parameter estimation demonstrated that both preferred orientation and tuning width were stable throughout the response to a single stimulus.

Prediction of orientation selectivity from receptive field architecture in simple cells of cat visual cortex.

From the intracellularly recorded responses to small, rapidly flashed spots, we have quantitatively mapped the receptive fields of simple cells in the cat visual cortex. We then applied these maps to a feedforward model of orientation selectivity. Both the preferred orientation and the width of orientation tuning of the responses to oriented stimuli were well predicted by the model. Where tested, the tuning curve was well predicted at different spatial frequencies. The model was also successful in predicting certain features of the spatial frequency selectivity of the cells. It did not successfully predict the amplitude of the responses to drifting gratings. Our results show that the spatial organization of the receptive field can account for a large fraction of the orientation selectivity of simple cells.

Membrane potential and conductance changes underlying length tuning of cells in cat primary visual cortex.

Spike responses for many cells of cat primary visual cortex are optimized for the length of a drifting grating stimulus. Stimuli that are longer or shorter than this optimal length elicit submaximal spike responses. To investigate the mechanisms responsible for this length tuning, we have recorded intracellularly from visual cortical neurons in the cat while presenting drifting grating stimuli of varying lengths. We have found that the membrane potential responses of the cells also exhibit length tuning, but that the suppression of spike responses at lengths longer than the preferred is 30-50% stronger than the corresponding suppression of the membrane potential responses. This difference may be attributed to the effects of spike threshold. Furthermore, using steady injected currents, we have measured changes in the excitatory and inhibitory components of input conductance evoked by stimuli of different lengths. We find that, compared with optimal stimuli, long stimuli evoke both an increase in inhibitory conductance and a decrease in excitatory conductance. These two mechanisms differ in their contrast sensitivity, resulting in stronger end stopping and shorter optimal lengths for high-contrast stimuli. These patterns suggest that response suppression for long stimuli is generated by a combination of active inhibition from stimuli outside the excitatory receptive field, as well as decreased excitation from other cortical cells that are themselves end-inhibited.

The contribution of noise to contrast invariance of orientation tuning in cat visual cortex.

Feedforward models of visual cortex appear to be inconsistent with a well-known property of cortical cells: contrast invariance of orientation tuning. The models' fixed threshold broadens orientation tuning as contrast increases, whereas in real cells tuning width is invariant with contrast. We have compared the orientation tuning of spike and membrane potential responses in single cells. Both are contrast invariant, yet a threshold-linear relation applied to the membrane potential accurately predicts the orientation tuning of spike responses. The key to this apparent paradox lies in the noisiness of the membrane potential. Responses that are subthreshold on average are still capable of generating spikes on individual trials. Unlike the iceberg effect, contrast invariance remains intact even as threshold narrows orientation selectivity. Noise may, by extension, smooth the average relation between membrane potential and spike rate throughout the brain.

Stimulus dependence of two-state fluctuations of membrane potential in cat visual cortex.

Membrane potentials of cortical neurons fluctuate between a hyperpolarized ('down') state and a depolarized ('up') state which may be separated by up to 30 mV, reflecting rapid but infrequent transitions between two patterns of synaptic input. Here we show that such fluctuations may contribute to representation of visual stimuli by cortical cells. In complex cells of anesthetized cats, where such fluctuations are most prominent, prolonged visual stimulation increased the probability of the up state. This probability increase was related to stimulus strength: its dependence on stimulus orientation and contrast matched each cell's averaged membrane potential. Thus large fluctuations in membrane potential are not simply noise on which visual responses are superimposed, but may provide a substrate for encoding sensory information.

Synchronous membrane potential fluctuations in neurons of the cat visual cortex.

We have recorded intracellularly from pairs of neurons less than 500 microm distant from one another in V1 of anesthetized cats. Cross-correlation of spontaneous fluctuations in membrane potential revealed significant correlations between the cells in each pair. This synchronization was not dependent on the occurrence of action potentials, indicating that it was not caused by mutual interconnections. The cells were synchronized continuously rather than for brief epochs. Much weaker correlations were found between the EEG and intracellular potentials, suggesting local, rather than global, synchrony. The highest correlation occurred among cells with similar connectivity from the LGN and similar receptive fields. During visual stimulation, correlations increased when both cells responded to the stimulus and decreased when neither cell responded.

Reduction of cortical pyramidal neuron excitability by the action of phenytoin on persistent Na+ current.

We examined the effect of the anticonvulsant phenytoin (PT) (20-200 microM) on the persistent Na+ current (INaP), INaP-dependent membrane potential responses and repetitive firing in layer 5 pyramidal neurons in a slice preparation of rat sensorimotor cortex. INaP measured directly with voltage-clamp was reduced in a concentration-dependent manner with an apparent EC50 value of 78 microM. Clear effects on current-evoked membrane potential responses were apparent at 50 microM PT: Subthreshold, depolarizing membrane potential rectification was reduced, rheobase current was increased and the relation between firing rate and injected current was shifted to the right, but action potential amplitude and duration were unaffected. We ascribed these effects of PT largely to the reduction of INaP. A slow decline of firing rate during the injected current pulse also became apparent at moderate PT concentrations. When PT concentration was raised to 150 to 200 microM, this slow adaption was enhanced markedly, and firing ceased during a sufficiently large current pulse. This enhanced slow adaptation and the cessation of firing were associated with a marked decline of spike amplitude and a rise in spike firing level during successive interspike intervals. We ascribe these effects largely to the action of PT on the transient Na+ current. We conclude that the reduction in cortical neuronal excitability by PT depends partly on its reduction of INaP, the effects of INaP blockade are apparent at PT concentrations lower than those required to abolish tonic firing and the cells need not be excessively depolarized for PT to decrease excitability by its effect on INaP.

Subthreshold oscillations and resonant behavior: two manifestations of the same mechanism.

The ability to generate subthreshold membrane potential oscillations in neurons from the inferior olive nucleus has been attributed to the electrical properties of these neurons, as well as to the properties of the network. In the present in vitro study we quantitatively characterized both intrinsic membrane and network properties that are directly involved in the oscillatory activity of olivary neurons in the guinea-pig. We also implemented an alternating current analysis to explore the resonance behavior of these neurons and to compare the resonant properties with the properties of the oscillatory activity. Spectral analysis, used for the quantitative characterization of the oscillatory activity under various experimental conditions, revealed that the pattern of the oscillatory activity is network specific rather than cell specific. These results are in agreement with the hypothesis that the oscillatory activity of olivary neurons is generated by a network of electrically coupled neurons. Using alternating current analysis, we found that impedance-frequency curves of olivary neurons demonstrate a peak impedance (resonance) at a frequency between 3 and 10 Hz, which corresponds to the frequency of the spontaneous oscillations. Like the spontaneous oscillations, this peak is tetrodotoxin insensitive, unaffected by K+ channel blockers and almost completely blocked in the presence of Ni2+ in the physiological solution. Increasing the temperature increases the resonance frequency, as well as the frequency of the spontaneous oscillations. These results show that the resonant behavior of individual neurons is the basis of the oscillatory behavior of the network and that resonance can serve as a lumped parameter which encodes the oscillatory tendency of a neuron.

Subthreshold oscillations of the membrane potential: a functional synchronizing and timing device.

1. Subthreshold membrane potential oscillations have been observed in different types of CNS neurons. In this in vitro study, we examined the possible role of these oscillations by analyzing the responses of neurons from the inferior olivary nucleus to a combined stimulation of sine wave and synaptic potentials. 2. A nonlinear summation of the sine wave and the synaptic potential occurred in olivary neurons; a superlinear summation occurred when the synaptic potential was elicited at the trough of the sine wave or during the rising phase. On the other hand, a less than linear summation occurred when the synaptic potentials were evoked during the falling phase of the wave. 3. Significant changes in the delay of the synaptic responses were observed. As a result of these changes, the maximum amplitude of the response occurred at the peak of the sine wave, regardless of the exact time of stimulation. The output of the neuron was therefore synchronized with the sine wave and depended only partly on the input phase. 4. These data demonstrate that neurons from the inferior olivary nucleus are capable of operating as accurate synchronizing devices. Moreover, by affecting the delay line, they act as a logic gate that ensures that the information will be added to the system only at given times.