Biology subjects

Disney, A. A.

Publications and source records attributed to Disney, A. A..

5 recordsLinked to original sources

bioRxiv2026

Perceptual performance and V1 neural activity are exquisitely sensitive to small changes in thalamocortical gain

In layer 4 of the primary sensory cortices, sensory data meets contextual information carried by modulatory systems, establishing a potentially important point of control. Accordingly, modulatory receptor expression at this point often differs from other nearby layers and cortical areas. Altering the processing state at even a small number of layer 4 thalamocortical synapses should be impactful on downstream processing, as this is the point at which most information about the outside world enters cortex. It is, however, often assumed--based on diffuse innervation of cortex by subcortical nuclei, and dense receptor expression in the association cortices--that modulatory signals are shared across large swaths of tissue, with the primary site of action being in higher levels of cortex. Hypothesizing that modifying the feedforward input to cortex might be an important capability of the cholinergic system, we recorded across the depth of cortex while delivering nicotine to a small proportion of thalamocortical synapses in macaque primary visual cortex, leveraging selective receptor expression to achieve spatial control. We observed bidirectional response changes throughout all layers, including layers in which nicotine is known to have no effect when applied locally. The pattern of these changes carried the signature of having passed through a normalizing circuit, rather than signatures of drug spread: the magnitude and tuning dependence of the response changes were well-accounted for by a normalization model with a tuned, multiplicative gain field. The circuit apparently did not compensate these changes; perceived contrast in a behavioral task was biased with the same normalization-predicted tuning dependence. SignificanceIn seeking to understand the role(s) neuromodulators play in cognition and behavior, answers are generally sought in the circuits of the association cortices, and neuromodulation is often conceived of, and modelled, in a manner akin to a coarse-grained--even cortex-wide--volume knob. Here, we show that focal cholinergic modulation of thalamocortical transmission in the visual system reshapes columnar neural activity and alters perceptual performance. Our observations suggest an underappreciated role for an old mechanistic concept: modulatory control of cortical gating.

neuroscience↗

bioRxiv2026

Calcium-binding protein expression alone is insufficient to identify and classify GABAergic neurons in macaque cortex

Understanding neuron subclasses and their functional consequences can contribute to understanding brain circuits. A scheme long used to classify GABAergic neurons in the neocortex is based on expression of three calcium-binding proteins (CBPs): parvalbumin (PV), calbindin D-28K (CB), and calretinin (CR). Because CB and CR are frequently co-expressed by individual neurons in rodents, this scheme has been replaced by one based on PV and two signaling peptides: somatostatin (SST) and vasoactive intestinal peptide (VIP). In macaques, however, CBPs are generally not co-expressed, and so their use has persisted despite suggestions that the underlying populations are not, in fact, entirely GABAergic. We set out to quantitatively evaluate CBPs as a classification scheme for GABAergic neurons in early and mid-level visual regions in macaque cortex. Combining immunohistochemistry and in situ hybridization, we find that up to half of neurons expressing CBPs are likely not GABAergic. Furthermore, contrary to what has been previously suggested, the GABAergic subpopulations cannot be distinguished based on staining intensity. Thus, the CBP-based classification scheme is not valid, at least as it has traditionally been used. Instead, we find support for co-labeling CB and CR neurons with SST and VIP, an approach that can identify GABAergic subpopulations within the CBP classes; or simply adopting the PV/SST/VIP scheme. We discuss the functional implications of expressing these various cell type markers, and how consideration of marker functions can support proper selection of a classification scheme for a given experimental purpose. Significance StatementThe findings of this study challenge the currently dominant classification scheme for GABAergic neurons in macaque cortex, a scheme based on expression of the calcium-binding proteins parvalbumin, calbindin D-28K, and calretinin. Specifically, we show that a large proportion of neurons that express protein or mRNA for these calcium-binding proteins are likely not GABAergic. We go on to consider alternative approaches, discussing under what circumstances each might be useful.

neuroscience↗

bioRxiv2019

Functional clusters of neurons in layer 6 of macaque V1

AbstracLayer 6 appears to perform a very important role in the function of macaque primary visual cortex, V1, but not enough is understood about the functional characteristics of neurons in the layer 6 population. It is unclear to what extent the population is homogeneous with respect to their visual properties or if one can identify distinct sub-populations. Here we performed a cluster analysis based on measurements of the responses of single neurons in layer 6 of primary visual cortex to achromatic grating stimuli that varied in orientation, direction of motion, spatial and temporal frequency, and contrast. The visual stimuli were presented in a stimulus window that was also varied in size. Using the responses to parametric variation in these stimulus variables we extracted a number of tuning response measures and used them in the cluster analysis. Six main clusters emerged along with some smaller clusters. Additionally we asked whether parameter distributions from each of the clusters were statistically different. There were clear separations of parameters between some of the clusters, particularly for f1/f0 ratio, direction selectivity, and temporal frequency bandwidth but other dimensions also showed differences between clusters. Our data suggest that in layer 6, across the spatial extent of a single cortical hypercolumn, there are multiple parallel circuits that provide information about different aspects of the visual stimulus.

neuroscience↗

bioRxiv2018

Most calbindin-immunoreactive neurons, but few calretinin-immunoreactive neurons, express the m1 acetylcholine receptor in the middle temporal visual area of the macaque monkey

Release of the neuromodulator acetylcholine into cortical circuits supports cognition, although its precise role and mechanisms of action are not well-understood. Little is known about functional differences in cholinergic modulatory effects across cortical model systems, but anatomical evidence suggests that such differences likely exist because, for example, the expression of cholinergic receptors differs profoundly both within and between species. In the primary visual cortex (V1) of macaque monkeys, cholinergic receptors are strongly expressed by inhibitory interneurons. Here, we examine m1 muscarinic acetylcholine receptor expression by two subclasses of inhibitory interneurons--identified by their expression of the calcium-binding proteins calbindin and calretinin--in the middle temporal extrastriate area (MT) of the macaque. Using dual-immunofluorescence confocal microscopy, we find that the majority of calbindin-immunoreative neurons (55%) and only few calretinin-immunoreactive neurons (10%) express the m1 acetylcholine receptor. This differs from the pattern observed in V1 of the same species, lending further support to the notion that cholinergic modulation in cortex is tuned such that different cortical compartments will respond to acetylcholine release in different ways.

neuroscience↗

bioRxiv2018

Variations in neuromodulatory chemical signatures define compartments in macaque cortex

Subcortical neuromodulatory systems exhibit widespread projections that influence the output of cortical circuits. These modulatory systems have been portrayed as providing global signals to the entirety of cortex based on their widespread innervation. This innervation is not necessarily predictive of the levels of the neuromodulatory molecules that actually provide these signals to cortex. In the present study, we examine tissue concentrations of dopamine, noradrenaline, and serotonin to see how they locally vary across multiple areas of the macaque cortex. Our results indicate that different cortical areas exhibit varying levels of dopamine, noradrenaline, and serotonin. Using cluster analysis, we examine how similar cortical regions are to each other, finding that similarities in neurochemical content are shared by areas that exhibit similar functionality. Altogether, these findings demonstrate that neurochemical signatures vary across cortical regions and help define unique, local neuromodulatory signaling compartments.

neuroscience↗