Baowang Li

The Derivation of Direction Selectivity in the Striate Cortex

In the central visual pathway of binocular animals, the property of directional selectivity (DS) is first exhibited in striate cortex. In this study, we sought to determine the neural circuitry underlying the transformation from non-DS neurons to DS cortical cells. In a well established model, DS receptive fields (RFs) are derived from the sum of two non-DS inputs with 90° (quadrature) spatiotemporal phase differences. We explored possible input sources for this model, which include non-DS simple cells and lateral geniculate nucleus (LGN) neurons, by examination of spatiotemporal RFs of single cells and of pairs of cells. We find that distributions of non-DS simple RFs do not match the temporal predictions of the quadrature model because of a lack of long-latency responses. The long-latency inputs could potentially arise from lagged LGN afferents. However, analysis of cell pairs indicates that DS cells receive cortical input from non-DS simple cells for both short- and long-latency components, with temporal phase differences typically <90°. Furthermore, the distribution of minimum phase differences needed to generate DS cells overlaps that exhibited by non-DS simple cells. Considered together, these results are consistent with a linear model whereby DS simple cells are formed from simple-cell inputs, with temporal phase differences often less than quadrature.

High-Resolution Neurometabolic Coupling in the Lateral Geniculate Nucleus

The relationships between neural and metabolic processes in activated brain regions are central to the interpretation of noninvasive imaging. To examine this relationship, we have used a specialized sensor to measure simultaneously tissue oxygen changes and neural activity in colocalized regions of the cats lateral geniculate nucleus (LGN). Previous work with this sensor has shown that a decrease or increase in tissue oxygen can be elicited by selective control of the location and extent of neural activation in the LGN. In the current study, to evaluate the temporal integration and homogeneity of neurometabolic coupling, we have determined the relationship between multiunit extracellular neural activity and tissue oxygen responses to visual stimuli of various durations and contrasts. Our results show that the negative but not the positive oxygen response changes in an approximately linear manner with stimulus duration. The relationship between the negative oxygen response and neural activity is relatively constant with stimulus duration. Moreover, both negative and positive oxygen responses saturate at high stimulus contrast levels. Coupling between neural activity and negative oxygen responses is well described by a power law function. These results help elucidate differences between the initial negative and subsequent positive metabolic responses and may be directly relevant to questions concerning brain mapping with functional magnetic resonance imaging.

Neurometabolic coupling between neural activity, glucose, and lactate in activated visual cortex.

Neural activity is closely coupled with energy metabolism but details of the association remain to be identified. One basic area involves the relationships between neural activity and the main supportive substrates of glucose and lactate. This is of fundamental significance for the interpretation of non‐invasive neural imaging. Here, we use microelectrodes with high spatial and temporal resolution to determine simultaneous co‐localized changes in glucose, lactate, and neural activity during visual activation of the cerebral cortex in the cat. Tissue glucose and lactate concentration levels are measured with electrochemical microelectrodes while neural spiking activity and local field potentials are sampled by a microelectrode. These measurements are performed simultaneously while neurons are activated by visual stimuli of different contrast levels, orientations, and sizes. We find immediate decreases in tissue glucose concentration and simultaneous increases in lactate during neural activation. Both glucose and lactate signals return to their baseline levels instantly as neurons cease firing. No sustained changes or initial dips in glucose or lactate signals are elicited by visual stimulation. However, co‐localized measurements of cerebral blood flow and neural activity demonstrate a clear delay in the cerebral blood flow signal such that it does not correlate temporally with the neural response. These results provide direct real‐time evidence regarding the coupling between co‐localized energy metabolism and neural activity during physiological stimulation. They are also relevant to a current question regarding the role of lactate in energy metabolism in the brain during neural activation.

Neurometabolic coupling differs for suppression within and beyond the classical receptive field in visual cortex

Non‐technical summary  In visual cortex, underlying neural circuits process images by decoding responses of cells to specific stimuli. The transducer for this process is the receptive field, i.e. the territory which enables a single neuron to be highly selective for visual stimuli. Suppression effects within and outside the receptive field serve to shape the selectivity by modulation of neural firing. We show here that oxygen metabolism decreases or increases, respectively, for suppression within or outside the receptive field. The difference in activity‐induced oxygen demand between the two types of suppression helps clarify the function of associated neural circuits.

Neurometabolic coupling in the lateral geniculate nucleus changes with extended age.

Attempts have been made in various studies to identify and trace changes in function in the aging visual system. Some results are conflicting and we report here a unique approach in an attempt to resolve selected issues. We have estimated neurometabolic coupling in the central visual pathway in young and old cats. Our technique provides high resolution simultaneous measurements of neuronal activity and changes in concentration of tissue oxygen in the thalamus of young and old cats. Following visual stimulation, we find shorter latency and time to peak in tissue oxygen responses in old compared with young animals. Estimates of local activity induced initial negative oxygen response show substantial reductions in older animals. Measurements of neural activity in the form of multiple unit activity are similar in the two age groups. To investigate the mechanisms underlying the changes in tissue oxygen response in older animals, we measured vascular capillary density and found it to be substantially lower in old than that in young animals. Together, these findings suggest that the changes in metabolic responses with age may be largely accounted for by alterations in the cerebral microvasculature rather than by changes in neural activity.

Spatial summation of neurometabolic coupling in the central visual pathway.

Noninvasive neural imaging has become an important tool in both applied and theoretical applications. The hemodynamic properties that are measured in functional magnetic resonance imaging (fMRI), for example, are generally used to infer neuronal characteristics. In an attempt to provide empirical data to connect the hemodynamic measurements with neural function, we have conducted previous studies in which neural activity and tissue oxygen metabolic functions are determined together in co-localized regions of the central visual pathway. A basic question in this procedure is whether oxygen responses are coupled linearly in space and time with neural activity. We have previously examined temporal factors, and in the current study, spatial characteristics are addressed. We have recorded from neurons in the lateral geniculate nucleus (LGN) and striate cortex in anesthetized cats. In both structures, there is a classical receptive field (CRF) within which a neuron can be activated. There is also a region outside the CRF from which stimulation cannot activate the cell directly but can influence the response elicited from the CRF. In this investigation we have used several specific spatial stimulus patterns presented to either the CRF or the surrounding region or to both areas together in order to determine spatial response patterns. Within the CRF, we find that neural and metabolic responses sum in a nonlinear fashion but changes in these two measurements are closely coupled. For stimuli that extend beyond the CRF, neural activity is generally reduced while oxygen response exhibits uncoupled changes.

Binocular activation elicits differences in neurometabolic coupling in visual cortex.

Non-invasive brain imaging requires comprehensive interpretation of hemodynamic signals. In functional magnetic resonance imaging, blood oxygen level dependent (BOLD) signals are used to infer neural processes. This necessitates a clear understanding of how BOLD signals and neural activity are related. One fundamental question concerns the relative importance of synaptic activity and spiking discharge. Although these two components are related, most previous work shows that synaptic activity is better reflected in the BOLD signal. However, the mechanisms of this relationship are not clear. The BOLD signal depends on relative changes in cerebral blood flow and cerebral metabolic rate of oxygen. Oxygen metabolism changes are difficult to measure with current imaging techniques, but it is possible to obtain direct quantitative simultaneous in vivo measurement of tissue oxygen and co-localized underlying neural activity. Here, we use this approach with a specific binocular stimulus protocol in order to activate inhibitory and excitatory neuronal pathways in the visual cortex. During excitatory binocular interaction, we find that metabolic, spiking, and local field potential responses are correlated. However, during suppressive binocular interaction, spiking activity and local field potentials (LFP) are dissociated while only the latter is coupled with metabolic response. These results suggest that inhibitory connections may be a key factor in the dissociation between LFP and spiking activity, which may contribute substantially to the close coupling between the BOLD signal and synchronized synaptic activity in the brain.