A spatially specified systems pharmacology therapy for axonal recovery after injury.

There are no known drugs or drug combinations that promote substantial central nervous system axonal regeneration after injury. We used systems pharmacology approaches to model pathways underlying axonal growth and identify a four-drug combination that regulates multiple subcellular processes in the cell body and axons using the optic nerve crush model in rats. We intravitreally injected agonists HU-210 (cannabinoid receptor-1) and IL-6 (interleukin 6 receptor) to stimulate retinal ganglion cells for axonal growth.

Information processing in the LGN: a comparison of neural codes and cell types.

To understand how anatomy and physiology allow an organism to perform its function, it is important to know how information that is transmitted by spikes in the brain is received and encoded. A natural question is whether the spike rate alone encodes the information about a stimulus (rate code), or additional information is contained in the temporal pattern of the spikes (temporal code). Here we address this question using data from the cat Lateral Geniculate Nucleus (LGN), which is the visual portion of the thalamus, through which visual information from the retina is communicated to the visual cortex.

How Far can Neural Correlations Reduce Uncertainty? Comparison of Information Transmission Rates for Markov and Bernoulli Processes.

The nature of neural codes is central to neuroscience. Do neurons encode information through relatively slow changes in the firing rates of individual spikes (rate code) or by the precise timing of every spike (temporal code)? Here we compare the loss of information due to correlations for these two possible neural codes. The essence of Shannon's definition of information is to combine information with uncertainty: the higher the uncertainty of a given event, the more information is conveyed by that event.

Synchrony can destabilize reward-sensitive networks.

When exposed to rewarding stimuli, only some animals develop persistent craving. Others are resilient and do not. How the activity of neural populations relates to the development of persistent craving behavior is not fully understood.

The biological basis of a universal constraint on color naming: cone contrasts and the two-way categorization of colors.

Many studies have provided evidence for the existence of universal constraints on color categorization or naming in various languages, but the biological basis of these constraints is unknown. A recent study of the pattern of color categorization across numerous languages has suggested that these patterns tend to avoid straddling a region in color space at or near the border between the English composite categories of "warm" and "cool". This fault line in color space represents a fundamental constraint on color naming.

Estimating the amount of information conveyed by a population of neurons.

Recent technological advances have made the simultaneous recording of the activity of many neurons common. However, estimating the amount of information conveyed by the discharge of a neural population remains a significant challenge. Here we describe our recently published analysis method that assists in such estimates.

Statistics of natural scenes and cortical color processing.

We investigate the spatial correlations of orientation and color information in natural images. We find that the correlation of orientation information falls off rapidly with increasing distance, while color information is more highly correlated over longer distances. We show that orientation and color information are statistically independent in natural images and that the spatial correlation of jointly encoded orientation and color information decays faster than that of color alone.

A generalized linear model of the impact of direct and indirect inputs to the lateral geniculate nucleus.

Relay neurons in the lateral geniculate nucleus (LGN) receive direct visual input predominantly from a single retinal ganglion cell (RGC), in addition to indirect input from other sources including interneurons, thalamic reticular nucleus (TRN), and the visual cortex. To address the extent of influence of these indirect sources on the response properties of the LGN neurons, we fit a Generalized Linear Model (GLM) to the spike responses of cat LGN neurons driven by spatially homogeneous spots that were rapidly modulated by a pseudorandom luminance sequence. Several spot sizes were used to probe the spatial extent of the indirect visual effects.

Estimating the amount of information carried by a neuronal population.

Although all brain functions require coordinated activity of many neurons, it has been difficult to estimate the amount of information carried by a population of spiking neurons. We present here a Fourier-based method for estimating the information delivery rate from a population of neurons, which allows us to measure the redundancy of information within and between functional neuronal classes. We illustrate the use of the method on some artificial spike trains and on simultaneous recordings from a small population of neurons from the lateral geniculate nucleus of an anesthetized macaque monkey.

Stimulus size dependence of information transfer from retina to thalamus.

Relay cells in the mammalian lateral geniculate nucleus (LGN) are driven primarily by single retinal ganglion cells (RGCs). However, an LGN cell responds typically to less than half of the spikes it receives from the RGC that drives it, and without retinal drive the LGN is silent (Kaplan and Shapley, 1984). Recent studies, which used stimuli restricted to the receptive field (RF) center, show that despite the great loss of spikes, more than half of the information carried by the RGC discharge is typically preserved in the LGN discharge (Sincich et al.

Improved mapping of information distribution across the cortical surface with the support vector machine.

The early visual cortices represent information of several stimulus attributes, such as orientation and color. To understand the coding mechanisms of these attributes in the brain, and the functional organization of the early visual cortices, it is necessary to determine whether different attributes are represented by different compartments within each cortex. Previous studies addressing this question have focused on the information encoded by the response amplitude of individual neurons or cortical columns, and have reached conflicting conclusions.

A simple model of retina-LGN transmission.

To gain a deeper understanding of the transmission of visual signals from retina through the lateral geniculate nucleus (LGN), we have used a simple leaky integrate and-fire model to simulate a relay cell in the LGN. The simplicity of the model was motivated by two questions: (1) Can an LGN model that is driven by a retinal spike train recorded as synaptic ('S') potentials, but does not include a diverse array of ion channels, nor feedback inputs from the cortex, brainstem, and thalamic reticular nucleus, accurately simulate the LGN discharge on a spike-for-spike basis? (2) Are any special synaptic mechanisms, beyond simple summation of currents, necessary to model experimental recordings? We recorded cat relay cell responses to spatially homogeneous small or large spots, with luminance that was rapidly modulated in a pseudo-random fashion. Model parameters for each cell were optimized with a Simplex algorithm using a short segment of the recording.

Hue maps in primate striate cortex.

The macaque striate cortex (V1) contains neurons that respond preferentially to various hues. The properties of these hue-selective neurons have been studied extensively at the single-unit level, but it is unclear how stimulus hue is represented by the distribution of activity across neuronal populations in V1. Here we use the intrinsic optical signal to image V1 responses to spatially uniform stimuli of various hues.

Brainstem input modulates globally the transmission through the lateral geniculate nucleus.

The transmission of visual information from the retina to the visual cortex through the lateral geniculate nucleus (LGN) is a complex process, which involves several neuronal mechanisms, elements, and circuits. The authors investigated this process in anesthetized, paralyzed cats by recording from LGN relay neurons, together with their retinal input, which appeared as slow (S) potentials. The major findings are: (1) The transfer ratio (LGN firing/retinal firing) fluctuated slowly and (2) these fluctuations in transfer ratio were synchronized across the nucleus, did not depend on visual stimulation, and were highly correlated with neural activity in the parabrachial nucleus of the brainstem (PBN).