Recent in vitro studies have shown that acetylcholine (ACh) selectively reduces the efficacy of lateral cortical connections via a muscarinic mechanism, while boosting the efficacy of thalamocortical/feed-forward connections via a nicotinic mechanism. This suggests that high levels of ACh should reduce center-surround interactions of neurons in primary visual cortex, making cells more reliant on feed-forward information. In line with this hypothesis, we show that local iontophoretic application of ACh in primate primary visual cortex reduced the extent of spatial integration, assessed by recording a neurons' length tuning. When ACh was externally applied, neurons' preferred length shifted toward shorter bars, showing reduced impact of the extra-classical receptive field. We fitted a difference and a ratio of Gaussian model to these data to determine the underlying mechanisms of this dynamic change of spatial integration. These models assume overlapping summation and suppression areas with different widths and gains to be responsible for spatial integration and size tuning. ACh significantly reduced the extent of the summation area, but had no significant effect on the extent of the suppression area. In line with previous studies, we also show that applying ACh enhanced the response in the majority of cells, especially in the later (sustained) part of the response. These findings are similar to effects of attention on neuronal activity. The natural release of ACh is strongly linked with states of arousal and attention. Our results may therefore be relevant to the neurobiological mechanism of attention.

Exposure of cortical cells to sustained sensory stimuli results in changes in the neuronal response function. This phenomenon, known as adaptation, is a common feature across sensory modalities. Here, we quantified the functional effect of adaptation on the ensemble activity of cortical neurons in the rat whisker-barrel system. A multishank array of electrodes was used to allow simultaneous sampling of neuronal activity. We characterized the response of neurons to sinusoidal whisker vibrations of varying amplitude in three states of adaptation. The adaptors produced a systematic rightward shift in the neuronal response function. Consistently, mutual information revealed that peak discrimination performance was not aligned to the adaptor but to test amplitudes 3-9 m higher. Stimulus presentation reduced single neuron trial-to-trial response variability (captured by Fano factor) and correlations in the population response variability (noise correlation). We found that these two types of variability were inversely proportional to the average firing rate regardless of the adaptation state. Adaptation transferred the neuronal operating regime to lower rates with higher Fano factor and noise correlations. Noise correlations were positive and in the direction of signal, and thus detrimental to coding efficiency. Interestingly, across all population sizes, the net effect of adaptation was to increase the total information despite increasing the noise correlation between neurons.

senting the orientation of features in the visual image is a fundamental operation of the early cortical visual system. The nature of such representations can be informed by considering anisotropic distributions of response across the range of orientations. Here we used functional MRI to study modulations in the cortical activity elicited by observation of a sinusoidal grating that varied in orientation. We report a significant anisotropy in the measured blood-oxygen leveldependent activity within visual areas V1, V2, V3, and V3A/B in which horizontal orientations evoked a reduced response. These visual areas and hV4 showed a further anisotropy in which increased responses were observed for orientations that were radial to the point of fixation. We speculate that the anisotropies in cortical activity may be related to anisotropies in the prevalence and behavioral relevance of orientations in typical natural environments. Although such studies considered pattern orientation independent of position in the visual field, anisotropic response distributions have been reported across the early human visual system when pattern orientation is specified relative to the local visual field meridian (Fig. 1). Specifically, responses are enhanced when the local pattern orientation is coincident with the angular meridian (radial) compared with when it is tangential (Clifford et al. 2009; Sasaki et al. 2006). An important consequence of this meridian-relative anisotropy is that it confers difficulties in the interpretation of putative anisotropies in field-independent pattern orientation, particularly when the stimulus (Furmanski and Engel 2000; Furmanski et al. 2004) or analysis (Serences et al. 2009; Yacoub et al. 2008) is restricted to a subregion of the visual field. In this circumstance, inferences about anisotropies in field-independent orientation can be confounded with those in meridian-relative orientation; for example, a stimulus restricted to the vertical visual field meridian will produce responses in which only the vertical fieldindependent orientation is also a radial meridian-relative orientation.The aim of this study was to measure the distribution of visual system responses to varied pattern orientation by considering both field-independent and meridian-relative indices. We used fMRI to measure the blood-oxygen level-dependent (BOLD) response to a sinusoidal grating that varied in orientation and to map the preferred visual field meridia from within the early retinotopic regions of human visual cortex. We report the presence of significant anisotropies to both field-independent and meridian-relative orientation from within visual areas V1, V2, V3, and V3A/B. Although the form of meridianrelative anisotropy is consistent with previous reports of a preference for radial orientations, the anisotropy in fieldindependent orientation is characterized by a reduced response to horizontal orientations. M E T H O D S SubjectsFour experienced psychophysical observers participated in this study. Each subject received a re...

Cortical processing is strongly influenced by the actions of neuromodulators such as acetylcholine (ACh). Early studies in anaesthetized cats argued that acetylcholine can cause a sharpening of orientation tuning functions and an improvement of the signal-to-noise ratio (SNR) of neuronal responses in primary visual cortex (V1). Recent in vitro studies have demonstrated that acetylcholine reduces the efficacy of feedback and intracortical connections via the activation of muscarinic receptors, and increases the efficacy of feed-forward connections via the activation of nicotinic receptors. If orientation tuning is mediated or enhanced by intracortical connections, high levels of acetylcholine should diminish orientation tuning. Here we investigate the effects of acetylcholine on orientation tuning and neuronal responsiveness in anaesthetized marmoset monkeys. We found that acetylcholine caused a broadening of the orientation tuning in the majority of cells, while tuning functions became sharper in only a minority of cells. Moreover, acetylcholine generally facilitated neuronal responses, but neither improved signal-to-noise ratio, nor reduced trial-to-trial firing rate variance systematically. Acetylcholine did however, reduce variability of spike occurrences within spike trains. We discuss these findings in the context of dynamic control of feed-forward and lateral/feedback connectivity by acetylcholine.

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