Biology subjects

Callaway, E.

Publications and source records attributed to Callaway, E..

5 recordsLinked to original sources

bioRxiv2024

High-Resolution Laminar Identification in Macaque Primary Visual Cortex Using Neuropixels Probes

Laminar electrode arrays allow simultaneous recording of activity of many cortical neurons and assignment to layers using current source density (CSD) analyses. Electrode arrays with 100-micron contact spacing have been used to estimate borders between layer 4 versus superficial or deep layers, but in macaque primary visual cortex (V1) there are far more layers, such as 4A which is only 50-100 microns thick. Neuropixels electrode arrays have 20-micron spacing, and thus could potentially discern thinner layers and more precisely identify laminar borders. Here we show that laminar distributions of CSDs lack consistency and the spatial resolution required for thin layers and accurate layer boundaries. To take full advantage of high density Neuropixels arrays, we have developed approaches based on higher resolution electrical signals and analyses, including spike waveforms and spatial spread, unit density, high-frequency action potential (AP) power spectrum, temporal power change, and coherence spectrum, that afford far higher resolution of laminar distinctions, including the ability to precisely detect the borders of even the thinnest layers of V1.

neuroscience↗

bioRxiv2023

Asymmetric cortical projections to striatal direct and indirect pathways distinctly control actions

The striatal direct and indirect pathways constitute the core for basal ganglia function in action control. Although both striatal D1- and D2-spiny projection neurons (SPNs) receive excitatory inputs from the cerebral cortex, whether or not they share inputs from the same cortical neurons, and how pathway-specific corticostriatal projections control behavior remain largely unknown. Here using a G-deleted rabies system in mice, we found that more than two-thirds of excitatory inputs to D2-SPNs also target D1-SPNs, while only one-third do so vice versa. Optogenetic stimulation of striatal D1- vs. D2-SPN-projecting cortical neurons differently regulate locomotion, reinforcement learning and sequence behavior, implying the functional dichotomy of pathway-specific corticostriatal subcircuits. These results reveal the partially segregated yet asymmetrically overlapping cortical projections on striatal D1- vs. D2-SPNs, and that the pathway-specific corticostriatal subcircuits distinctly control behavior. It has important implications in a wide range of neurological and psychiatric diseases affecting cortico-basal ganglia circuitry. In BriefKlug, Yan et al. employed a modified rabies system in combination with slice physiology, optogenetics and behavioral tests to reveal that pathway-specific corticostriatal subcircuits distinctly control actions. HighlightsO_LIOne-third of the excitatory inputs to D1-SPNs project to D2-SPNs, while two-third of the excitatory inputs to D2-SPNs also target D1-SPNs C_LIO_LIActivation of D1-SPN projecting cortical neurons triggers behavioral effects in line with postsynaptic striatal direct pathway activation C_LIO_LIActivation of D2-SPN projecting cortical neurons causes behavioral effects similar with co-activation of both direct and indirect pathways C_LIO_LICorticostriatal subcircuits control actions in a brain-region and pathway-specific manner C_LI

neuroscience↗

bioRxiv2023

Parallel pathways carrying direction and orientation selective retinal signals to layer 4 of mouse visual cortex

Parallel functional and anatomical visual pathways from the retina to primary visual cortex (V1) via the lateral geniculate nucleus (LGN) are common to many mammalian species, including mice, carnivores and primates. However, the much larger number of retinal ganglion cell (RGC) types that project to the LGN, as well as the more limited lamination of both the LGN and the thalamocortical-recipient layer 4 (L4) in mice, leaves considerable uncertainty about which visual features present in both retina and V1 might be inherited from parallel pathways versus extracted by V1 circuits in the mouse visual system. Here, we explored the relationships between functional properties of L4 V1 neurons and their RGC inputs by taking advantage of two Cre-expressing mouse lines -- Nr5a1-Cre and Scnn1a-Tg3-Cre -- that each label functionally and anatomically distinct populations of L4 neurons. Visual tuning properties of L4 V1 neurons were evaluated using Cre-dependent expression of GCaMP6s followed by 2-photon calcium imaging. RGCs providing input to these neurons (via LGN) were labeled and characterized using Cre-dependent trans-synaptic retrograde labeling with G-deleted rabies virus. We find significant differences in the tuning of Nr5a1-Cre versus Scnn1a-Tg3-Cre neurons for direction, orientation, spatial frequency, temporal frequency, and speed. Strikingly, a subset of the RGCs had tuning properties that matched the direction and orientation tuning properties of the L4 V1 neurons to which they provided input. Altogether, these results suggest that direction and orientation tuning of V1 neurons may be at least partly inherited from parallel pathways originating in the retina.

neuroscience↗

bioRxiv2023

Microbially-derived indole-3-acetate alleviates diet induced steatosis and inflammation in mice

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. There is growing evidence that dysbiosis of the intestinal microbiota and disruption of microbiota-host interactions contribute to the pathology of NAFLD. We previously demonstrated that gut microbiota derived tryptophan metabolite indole-3-acetate (I3A) was decreased in both cecum and liver of high-fat diet-fed mice and attenuated the expression of inflammatory cytokines in macrophages and TNF-a and fatty acid induced inflammatory responses in an aryl-hydrocarbon receptor (AhR) dependent manner in hepatocytes. In this study, we investigated the effect of orally administered I3A in a mouse model of diet induced NAFLD. Western diet (WD)-fed mice given sugar water (SW) with I3A showed dramatically decreased serum ALT, hepatic TG, liver steatosis, hepatocyte ballooning, lobular inflammation, and hepatic production of inflammatory cytokines, compared to WD-fed mice given only SW. Metagenomic analysis show that I3A administration did not significantly modify the intestinal microbiome, suggesting that I3As beneficial effects likely reflect the metabolites direct actions on the liver. Administration of I3A partially reversed WD induced alterations of liver metabolome and proteome, notably, decreasing expression of several enzymes in hepatic lipogenesis and {beta}- oxidation. Mechanistically, we also show that AMP-activated protein kinase (AMPK) mediates the anti-inflammatory effects of I3A in macrophages. The potency of I3A in alleviating liver steatosis and inflammation clearly demonstrates its potential as a therapeutic modality for preventing the progression of steatosis to NASH.

cell biology↗

bioRxiv2022

Quantification of Monosynaptic Rabies Tracing Efficiency

Retrograde monosynaptic tracing using glycoprotein-deleted rabies virus is an important component of the toolkit for investigation of neural circuit structure and connectivity. It allows for the identification of first-order presynaptic connections to cell populations of interest across both the central and peripheral nervous system, helping to decipher the complex connectivity patterns of neural networks that give rise to brain function. Despite its utility, the efficiency with which genetically modified rabies virus spreads retrogradely across synapses remains uncertain. While past studies have revealed conditions that can increase or decrease the numbers of presynaptic cells labeled, it is unknown what proportion of total inputs to a starter cell of interest are labeled. It is also unknown whether synapses that are more proximal or distal to the cell body are labeled with different efficiencies. Here we use a new rabies virus construct that allows for the simultaneous labeling of pre and postsynaptic specializations to quantify efficiency of spread at the synaptic level in mouse primary visual cortex. We demonstrate that with typical conditions about 40% of first-order presynaptic excitatory inputs are labeled. We show that using matched tracing conditions there is similar efficiency of spread from excitatory or inhibitory starter cell types. Furthermore, we find no difference in the efficiency of labeling of excitatory inputs to postsynaptic sites at different subcellular locations.

neuroscience↗