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Edward M Callaway

Publications and source records attributed to Edward M Callaway.

At least 19 recordsLinked to original sources
PubMed2025

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.

Journal Article↗
PubMed2006

Retrograde neuronal tracing with a deletion-mutant rabies virus.

We have constructed a deletion-mutant rabies virus encoding EGFP and find it to be an excellent tool for studying detailed morphology and physiology of neurons projecting to injection sites within the mammalian brain. The virus cannot spread beyond initially infected cells yet, unlike other viral vectors, replicates its core within them. The cells therefore fluoresce intensely, revealing fine dendritic and axonal structure with no background from partially or faintly labeled cells.

Animals↗
PubMed2006

Multiple circuits relaying primate parallel visual pathways to the middle temporal area.

Parallel pathways in the primate visual system parse the sensory signal into magnocellular (M), parvocellular (P), and koniocellular (K) streams. These pathways remain anatomically separate and distinct from their origination in different retinal ganglion cell types, through distinct layers of the lateral geniculate nucleus, and into primary visual cortex (V1), with the M pathway terminating primarily in layer 4Calpha, the P pathway in layer 4Cbeta, and the K pathway in the cytochrome oxidase blobs of layer 2/3. Recent studies indicate that outputs from V1 are less compartmental than previously thought, making it difficult to assess the contributions of M and P pathways to areas beyond V1 in the dorsal and ventral streams. Here we use rabies virus as a retrograde transsynaptic tracer to study the contributions of M and P pathways to areas middle temporal (MT), V3, and V2 of macaque monkey. We find that, although disynaptic inputs through layer 4C of V1 to dorsal stream area MT are dominated by the M pathway, within an additional three synapses MT receives a substantial P input. This P input is unlikely to reach MT via V3, which we show also receives disynaptic inputs dominated by the M pathway. We find that disynaptic inputs to V2, however, can be more balanced and may carry convergent M and P input to MT. Our observations provide evidence for multiple pathways from V1 to MT, with varying degrees of M and P convergence. Each pathway likely provides functionally specialized information to MT and dorsal stream visual processing.

Animals↗
PubMed2006

Mouse cortical inhibitory neuron type that coexpresses somatostatin and calretinin.

Mammalian cortex contains a diversity of inhibitory neuron types, each with distinct morphological, immunochemical, and/or physiological properties. In rat cortex, chemical markers distinguish at least four distinct and nonoverlapping neuron classes based on expression of parvalbumin (PV), somatostatin (SST), calretinin (CR), and cholecystokinin (CCK). It has generally been assumed that these classifications should also apply to other rodent species. In mouse cortex, however, we found significant colocalization of SST and CR in inhibitory neurons; about 30% of SST-positive cells contained CR, and about 33% of CR-positive cells contained SST across frontal, somatosensory (S1), and visual cortex (V1). The SST and CR colocalized cells were concentrated in layer 2/3. We further characterized morphological and physiological properties of the mouse cortical inhibitory neuron types that express SST by using "GIN" transgenic mice, in which GFP is expressed in a subset of SST inhibitory neurons (see Oliva et al. [2000] J Neurosci 20:3354-3368). Generally, both SST/CR+ cells and SST/CR- cells exhibited morphological features of Martinotti cells as described in rat cortex, and they also had similar accommodating spike-firing patterns. However, they differed significantly in quantitative comparisons of morphology and spike shapes. SST/CR+ cells had more horizontally extended dendritic fields and more primary process than did SST/CR- cells; and SST/CR- cells had narrower action potential widths and faster afterhyperpolarization than did SST/CR+ cells. Thus, our data show an important species difference in the chemical distinction of inhibitory neuron subtypes, and indicate that colocalization of CR in SST cells correlates with different morphological and physiological features.

Action Potentials↗
PubMed2006

Visual spatial summation in macaque geniculocortical afferents.

The spatial summation properties of visual signals were analyzed for geniculocortical afferents in the primary visual cortex (V1) of anesthetized paralyzed macaque monkeys. Afferent input responses were recorded extracellularly during cortical inactivation through superfusion of the cortex with muscimol, allowing investigation of lateral geniculate nucleus of the thalamus (LGN) cell properties in the absence of cortical feedback. Responses from afferent inputs were classified as magno-, parvo-, or koniocellular based on anatomical organization within the cortex, established through histological reconstructions, and visual response wavelength sensitivity. More than 80% of afferents showed strong surround suppression [suppression index (SI) >0.5] and 14% showed negligible surround suppression (SI < 0.2). Afferent responses with weak and strong surround suppression were found throughout cortical input layers 4C and 4A. High-contrast estimates of the spatial extent of the classical surround were similar to the nonclassical surround. The classical and nonclassical surrounds were, on average, 1.5-fold larger than the excitatory center. Unlike neurons within V1, the spatial extent of excitatory summation for geniculocortical afferents was contrast invariant. Nonclassical surround suppression showed slight contrast dependency with estimates larger (20%) at lower contrasts and stronger at higher contrasts (13%). Surround suppression is inherent in cortical input responses and likely derives from lateral inhibition in either the LGN or retina. Although surround suppression within afferent responses increases slightly with contrast, the spatial spread of excitation remains fixed with contrast. This argues for distinct mechanisms of action for contrast-dependent modulation in cortical and subcortical responses.

Action Potentials↗
PubMed2006

Selective and quickly reversible inactivation of mammalian neurons in vivo using the Drosophila allatostatin receptor.

Genetic strategies for perturbing activity of selected neurons hold great promise for understanding circuitry and behavior. Several such strategies exist, but there has been no direct demonstration of reversible inactivation of mammalian neurons in vivo. We previously reported quickly reversible inactivation of neurons in vitro using expression of the Drosophila allatostatin receptor (AlstR). Here, adeno-associated viral vectors are used to express AlstR in vivo in cortical and thalamic neurons of rats, ferrets, and monkeys. Application of the receptor's ligand, allatostatin (AL), leads to a dramatic reduction in neural activity, including responses of visual neurons to optimized visual stimuli. Additionally, AL eliminates activity in spinal cords of transgenic mice conditionally expressing AlstR. This reduction occurs selectively in AlstR-expressing neurons. Inactivation can be reversed within minutes upon washout of the ligand and is repeatable, demonstrating that the AlstR/AL system is effective for selective, quick, and reversible silencing of mammalian neurons in vivo.

Action Potentials↗
PubMed2006

The parvocellular LGN provides a robust disynaptic input to the visual motion area MT.

Dorsal visual cortical areas are thought to be dominated by input from the magnocellular (M) visual pathway, with little or no parvocellular (P) contribution. These relationships are supported by a close correlation between the functional properties of these areas and the M pathway and by a lack of anatomical evidence for P input. Here we use rabies virus as a retrograde transynaptic tracer to show that the dorsal area MT receives strong input, via a single relay, from both M and P cells of the lateral geniculate nucleus. This surprising P input, likely relayed via layer 6 Meynert cells in primary visual cortex, can provide MT with sensitivity to a more complete range of spatial, temporal, and chromatic cues than the M pathway alone. These observations provide definitive evidence for P pathway input to MT and show that convergence of parallel visual pathways occurs in the dorsal stream.

Animals↗
PubMed2006

Should I stay or should I go? Presynaptic boutons in the adult cortex still haven't made up their minds.

Previous studies demonstrating turnover of the dendritic spines of cortical neurons have suggested a modest rate of turnover of synaptic connections. Now, two papers in this issue of Neuron address this question from the other side of the synapse, the presynaptic boutons. Both studies use in vivo multiphoton imaging of cortical axons to show that synaptic boutons come and go, just like spines. One of the studies shows remarkable diversity in the lability of boutons depending on the cell type from which they originate, with some boutons displaying nearly complete turnover in just a few months. The other study shows that bouton turnover occurs in primates as well as rodents.

Animals↗
PubMed2006

V1 spinal neurons regulate the speed of vertebrate locomotor outputs.

The neuronal networks that generate vertebrate movements such as walking and swimming are embedded in the spinal cord. These networks, which are referred to as central pattern generators (CPGs), are ideal systems for determining how ensembles of neurons generate simple behavioural outputs. In spite of efforts to address the organization of the locomotor CPG in walking animals, little is known about the identity and function of the spinal interneuron cell types that contribute to these locomotor networks. Here we use four complementary genetic approaches to directly address the function of mouse V1 neurons, a class of local circuit inhibitory interneurons that selectively express the transcription factor Engrailed1. Our results show that V1 neurons shape motor outputs during locomotion and are required for generating 'fast' motor bursting. These findings outline an important role for inhibition in regulating the frequency of the locomotor CPG rhythm, and also suggest that V1 neurons may have an evolutionarily conserved role in controlling the speed of vertebrate locomotor movements.

Action Potentials↗
PubMed2006

Development of layer-specific axonal arborizations in mouse primary somatosensory cortex.

In the developing neocortex, pyramidal neurons use molecular cues to form axonal arbors selectively in the correct layers. Despite the utility of mice for molecular and genetic studies, little work has been done on the development of layer-specific axonal arborizations of pyramidal neurons in mice. We intracellularly labeled and reconstructed the axons of layer 2/3 and layer 5 pyramidal neurons in slices of primary somatosensory cortex from C57Bl6 mice on postnatal days 7-21. For all neurons studied, the development of the axonal arborizations in mice follows a pattern similar to that seen in other species; laminar specificity of the earliest axonal branches is similar to that of mature animals. At P7, pyramidal neurons are very simple, having only a main descending axon and few primary branches. Between P7 and P10, there is a large increase in the total number of axonal branches, and axons continue to increase in complexity and total length from P10 to P21. Unlike observations in ferrets, cats, and monkeys, two types of layer 2/3 pyramidal neurons are present in both mature and developing mice; cells in superficial layer 2/3 lack axonal arbors in layer 4, and cells close to the layer 4 border have substantial axonal arbors within layer 4. We also describe axonal and dendritic arborization patterns of three pyramidal cell types in layer 5. The axons of tall-tufted layer 5 pyramidal neurons arborize almost exclusively within deep layers while tall-simple, and short layer 5 pyramidal neurons also project axons to superficial layers.

Animals↗
PubMed2005

In vivo evidence for radial migration of neurons by long-distance somal translocation in the developing ferret visual cortex.

During the development of the cerebral cortex, neurons generated in the cortical ventricular zone migrate radially toward the marginal zone. Radially migrating neurons are thought to display 1 of 2 morphologies: cells with a long, pia-contacting, apical process utilized for somal translocation early in development, when the cortex is still relatively thin; or cells with a short leading process, abundant at late stages of corticogenesis when neurons need to travel for longer distances. In large convoluted brains, like those of many primates and carnivores, radially migrating neurons must travel distances up to several millimeters before reaching their final destination, often following curvilinear trajectories. Here we analyze modes and morphologies of radially migrating neurons in convoluted brains by studying the visual cortex of developing ferrets. We provide in vivo and in vitro evidence for the existence of late-born cortical neurons that migrate radially by long-distance somal translocation within a long apical process extended to the cortical plate, in contrast to the early somal translocation observed in rodents. Long-distance translocating neurons in the ferret show a discontinuous rhythm of migration, alternating periods of advance with periods of stall. Furthermore, by combining different labeling methods we find the simultaneous presence in the developing ferret cortex of long-distance translocating neurons and neurons migrating within a short leading process.

Adenoviridae↗
PubMed2005

Local connections to specific types of layer 6 neurons in the rat visual cortex.

Because layer 6 of the cerebral cortex receives direct thalamic input and provides projections back to the thalamus, it is in a unique position to influence thalamocortical interactions. Different types of layer 6 pyramidal neurons provide output to different thalamic nuclei, and it is therefore of interest to understand the sources of functional input to these neurons. We studied the morphologies and local excitatory input to individual layer 6 neurons in rat visual cortex by combining intracellular labeling and recording with laser-scanning photostimulation. As in previous photostimulation studies, we found significant differences in the sources of local excitatory input to different cell types. Most notably, there were differences in local input to neurons that, based on analogy to barrel cortex, are likely to project only to the lateral geniculate nucleus of the thalamus versus those that are likely to also project to the lateral posterior nucleus. The more striking finding, however, was the paucity of superficial layer input to layer 6 neurons in the rat visual cortex, contrasting sharply with layer 6 neurons in the primate visual cortex. These observations provide insight into differences in function between cortical projections to first-order versus higher-order thalamic nuclei and also show that these circuits can be organized differently in different species.

Animals↗
PubMed2005

Fine-scale specificity of cortical networks depends on inhibitory cell type and connectivity.

Excitatory cortical neurons form fine-scale networks of precisely interconnected neurons. Here we tested whether inhibitory cortical neurons in rat visual cortex might also be connected with fine-scale specificity. Using paired intracellular recordings and cross-correlation analyses of photostimulation-evoked synaptic currents, we found that fast-spiking interneurons preferentially connected to neighboring pyramids that provided them with reciprocal excitation. Furthermore, they shared common fine-scale excitatory input with neighboring pyramidal neurons only when the two cells were reciprocally connected, and not when there was no connection or a one-way, inhibitory-to-excitatory connection. Adapting inhibitory neurons shared little or no common input with neighboring pyramids, regardless of their direct connectivity. We conclude that inhibitory connections and also excitatory connections to inhibitory neurons can both be precise on a fine scale. Furthermore, fine-scale specificity depends on the type of inhibitory neuron and on direct connectivity between neighboring pyramidal-inhibitory neuron pairs.

Action Potentials↗
PubMed2005

Structure and function of parallel pathways in the primate early visual system.

Parallel processing streams in the primate visual system originate from more than a dozen anatomically and functionally distinct types of retinal ganglion cells (RGCs). A central problem in determining how visual information is processed is understanding how each of these RGC types connects to more central structures, including the lateral geniculate nucleus (LGN) of the thalamus and (via the LGN) the primary visual cortex. Nevertheless, the available functional and anatomical evidence linking together specific cell types across these structures is surprisingly indirect. This review evaluates the available evidence and assesses the strength of the many inferences that can be made from these observations. There is strong evidence that parasol RGCs are the provenance of the magnocellular (M) visual pathway and that midget RGCs give rise to the parvocellular (P) pathway. Furthermore, the M and P pathways remain segregated up to the input layer of primary visual cortex. The relationships between the numerous other RGC types and cell types in the LGN remain less certain. and there remains ambiguity about how best to define additional pathways, such as the koniocellular (K) pathway, which probably arise from these other, less common, RGC types.

Action Potentials↗
PubMed2005

Redefining the boundaries of the hippocampal CA2 subfield in the mouse using gene expression and 3-dimensional reconstruction.

The morphology of neurons in the main divisions of the hippocampal complex allow the easy identification of granule cells in the dentate gyrus and pyramidal cells in the CA1 and CA3 regions of Ammon's horn. However, neurons in the CA2 subfield have been much more difficult to reliably identify. We have recently identified a set of genes whose expression is restricted to either the dentate gyrus, CA1, CA2, or CA3. Here we show that these genes have an essentially nonoverlapping distribution throughout the entire septotemporal extent of the hippocampus. 3-Dimensional reconstruction of serial sections processed for in situ hybridization of mannosidase 1, alpha (CA1), bcl-2-related ovarian killer protein (CA3), and Purkinje cell protein 4 (dentate gyrus+CA2) was used to define the boundaries of each subregion throughout the entire hippocampus. The boundaries observed for these three genes are recapitulated across a much larger set of genes similarly enriched in specific hippocampal subregions. The extent of CA2 defined on the basis of gene expression is somewhat larger than that previously described on the basis of structural anatomical criteria, particularly at the rostral pole of the hippocampus. These results indicate that, at least at the molecular level, there are robust, consistent genetic boundaries between hippocampal subregions CA1, CA2, CA3, and the dentate gyrus, allowing a redefinition of their boundaries in order to facilitate functional studies of different neuronal subtypes in the hippocampus.

Animals↗
PubMed2005

Excitatory cortical neurons form fine-scale functional networks.

The specificity of cortical neuron connections creates columns of functionally similar neurons spanning from the pia to the white matter. Here we investigate whether there is an additional, finer level of specificity that creates subnetworks of excitatory neurons within functional columns. We tested for fine-scale specificity of connections to cortical layer 2/3 pyramidal neurons in rat visual cortex by using cross-correlation analyses of synaptic currents evoked by photostimulation. Recording simultaneously from adjacent layer 2/3 pyramidal cells, we find that when they are connected to each other (20% of all recorded pairs) they share common input from layer 4 and within layer 2/3. When adjacent layer 2/3 neurons are not connected to each other, they share very little (if any) common excitatory input from layers 4 and 2/3. In contrast, all layer 2/3 neurons share common excitatory input from layer 5 and inhibitory input from layers 2/3 and 4, regardless of whether they are connected to each other. Thus, excitatory connections from layer 4 to layer 2/3 and within layer 2/3 form fine-scale assemblies of selectively interconnected neurons; inhibitory connections and excitatory connections from layer 5 link neurons across these fine-scale subnetworks. Relatively independent subnetworks of excitatory neurons are therefore embedded within the larger-scale functional architecture; this allows neighbouring neurons to convey information more independently than suggested by previous descriptions of cortical circuitry.

Action Potentials↗
PubMed2005

A molecular and genetic arsenal for systems neuroscience.

Neural circuits are composed of a meshwork of numerous neuron types, each with their own distinctive morphological and intrinsic physiological properties, connectivity and biochemistry. How do distinct neural subcircuits, composed of different classes of neuron, contribute to brain function? Approaching this question requires methods that can target specific neurons types. This can be achieved by harnessing the same machinery that builds sophistication into the brain and using it to make novel tools for investigating and manipulating the brain: molecular and genetic technology. These tools can be used to target gene expression to specific neuron types within complicated neuronal circuits, and the transgenes that are expressed can be used to elucidate and manipulate these circuits with unprecedented precision and control. These methods are likely to become the archetype for future studies linking perception, cognition and behavior to specific components of the brain.

Animals↗