Extraction of the average and differential dynamical response in stimulus-locked experimental data.

In optical imaging experiments of primary visual cortex, visual stimuli evoke a complicated dynamics. Typically, any stimulus with sufficient contrast evokes a response. Much of the response is the same regardless of which stimulus is presented. For instance, when oriented drifting gratings are presented to the visual system, over 90% of the response is the same from orientation to orientation. Small differences may be seen, however, between the responses to different orientations. A problem in the analysis of optical measurements of the response to stimulus in cortical tissue is the distinction of the 'global' or 'non-specific' response from the 'differential' or 'stimulus-specific' response. This problem arises whenever the signal of interest is the difference in response to various stimuli and is evident in many kinds of uni- and multivariate data. To this end, we present enhancements to a frequency-based method that we previously introduced called the periodic stacking method. These enhancements allow us to separately estimate the dynamics of both the average signal across all stimuli (the 'global' response) and deviations from the average amongst the various stimuli (the 'stimulus-specific' response) evoked in response to a set of stimuli. We also discuss improvements in the signal-to-noise ratio, relative to standard trial averaging methods, that result from the data-adaptive smoothing in our method.

Spatiotemporal analysis of optical imaging data.

Previous methods for analyzing optical imaging data have relied heavily on temporal averaging. However, response dynamics are rich sources of information. Here, we develop and present a method that combines principal component analysis and multitaper harmonic analysis to extract the statistically significant spatial and temporal response from optical imaging data. We apply the method to both simulated data and experimental optical imaging data from the cat primary visual cortex.

Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways.

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons.

Signal transduction differences between 5-hydroxytryptamine type 2A and type 2C receptor systems.

The cDNAs for human 5-hydroxytryptamine (5-HT)2C and 5-HT2A receptors were stably transfected separately into parent Chinese hamster ovary cells, and cell lines in which levels of transfected receptor protein expression and accumulation of inositol phosphates in response to 5-HT were comparable were chosen for study. The effect of activation of these receptors on 5-HT1B-like receptor-mediated responsiveness (i.e., inhibition of forskolin-stimulated cAMP accumulation) was studied. Activation of 5-HT2C receptors with 5-HT (0.1-100 microM) abolished the 5-HT1B-like response, which returned when 5-HT2C receptors were blocked with mesulergine (1 microM). Furthermore, the maximal response to 5-carboxytryptamine was reduced in a concentration-dependent manner by the 5-HT2A/5-HT2C-selective partial agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. In contrast, activation of 5-HT2A receptors with either 5-HT or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane did not alter the 5-HT1B-like response. The reduction of 5-HT1B-like responsiveness produced by 5-HT2C receptor activation was independent of protein kinase C activation and increases in the intracellular calcium concentration. Although 5-HT2A and 5-HT2C receptors are strikingly similar in structure and pharmacology, and the signal transduction systems coupled to these receptors have been thought to be similar, if not identical, these data provide the first evidence for fundamental differences in the signal transduction systems of these 5-HT2 receptor subtypes.