Removal of sensory input from a focal region of adult neocortex can lead to a large reorganization of cortical topography within the deprived area during subsequent months. Although this form of functional recovery is now well documented across several sensory systems, the underlying cellular mechanisms remain elusive. Weeks after binocular retinal lesions silence a corresponding portion of striate cortex in the adult cat, this cortex again becomes responsive, this time to retinal loci immediately outside the scotoma. Earlier findings showed a lack of reorganization in the lateral geniculate nucleus and an inadequate spread of geniculocortical afferents to account for the cortical reorganization, suggesting the involvement of intrinsic cortical connections. We investigated the possibility that intracortical axonal sprouting mediates long-term reorganization of cortical functional architecture. The anterograde label biocytin was used to compare the density of lateral projections into reorganized and non-deprived cortex. We report here that structural changes in the form of axonal sprouting of long-range laterally projecting neurons accompany topographic remodelling of the visual cortex.

In primary sensory and motor cortex of adult animals, alteration of input from the periphery leads to changes in cortical topography. These changes can be attributed to processes that are intrinsic to the cortex, or can be inherited from alterations occurring at stages of sensory processing that are antecedent to the primary sensory cortical areas. In the visual system, focal binocular retinal lesions initially silence an area of cortex that represents the region of retina destroyed, but over a period of months this area recovers visually driven activity. The retinotopic map in the recovered area is altered, shifting its representation to the portion of retina immediately surrounding the lesion. This effectively shrinks the representation of the lesioned area of retina, and expands the representation of the lesion surround. To determine the loci along the visual pathway at which the reorganization takes place, we compared the course of topographic alterations in the primary visual cortex and dorsal lateral geniculate nucleus (LGN) of cats and monkeys. At a time when the cortical reorganization is complete, the silent area of LGN persists, indicating that changes in cortical topography are due to alterations that are intrinsic to the cortex. To explore the participation of thalamocortical afferents in the reorganization, we injected a series of retrogradely transported fluorescent tracers into reorganized and surrounding cortex of each animal. Our results show that the thalamocortical arbors do not extend beyond their normal lateral territory and that this physical dimension is insufficient to account for the reorganization. We suggest that the long-range intrinsic horizontal connections are a likely source of visual input into the reorganized cortical area.

We used several fluorescent dyes (Fast Blue, Diamidino Yellow, Rhodamine Latex Microspheres, Evans Blue, and Fluoro-Gold) in each of eight macaques, to examine the patterns of thalamic input to the sensorimotor cortex of macaques 12 months or older. Inputs to different zones of motor, premotor, and postarcuate cortex, supplementary motor area, and areas 3b/1 and 2/5 in the postcentral cortex, were examined. Coincident labeling of thalamocortical neuron populations with different dyes (1) increased the precision with which their soma distributions could be related within thalamic space, and (2) enabled the detection by double labeling, of individual thalamic neurons that were common to the thalamic soma distributions projecting to separate, dye-injected cortical zones. Double-labeled thalamic neurons projecting to sensorimotor cortex were rarely seen in mature macaques, even when the injection sites were only 1-1.5 mm apart, implying that their terminal arborizations were quite restricted horizontally. By contrast, separate neuron populations in each thalamic nucleus with input to sensorimotor cortex projected to more than one cytoarchitecturally distinct cortical area. In ventral posterior lateral (oral) (VPLo), for example, separate populations of cells sent axons to precentral medial, and lateral area 4, medial premotor, and postarcuate cortex, as well as to supplementary motor area. Extensive convergence of thalamic input even to the smallest zones of dye uptake in the cortex (approximately 0.5 mm3) characterized the sensorimotor cortex. The complex forms of these projection territories were explored using 3-dimensional reconstructions from coronal maps. These projection territories, while highly ordered, were not contained by the cytoarchitectonic boundaries of individual thalamic nuclei. Their organization suggests that the integration of the diverse information from spinal cord, cerebellum, and basal ganglia that is needed in the execution of complex sensorimotor tasks begins in the thalamus.

Hibernating mammals are remarkable for surviving near-freezing brain temperatures and near cessation of neural activity for a week or more at a time. This extreme physiological state is associated with dendritic and synaptic changes in hippocampal neurons. Here, we investigate whether these changes are a ubiquitous phenomenon throughout the brain that is driven by temperature. We iontophoretically injected Lucifer yellow into several types of neurons in fixed slices from hibernating ground squirrels. We analyzed neuronal microstructure from animals at several stages of torpor at two different ambient temperatures, and during the summer. We show that neuronal cell bodies, dendrites, and spines from several cell types in hibernating ground squirrels retract on entry into torpor, change little over the course of several days, and then regrow during the 2 h return to euthermia. Similar structural changes take place in neurons from the hippocampus, cortex, and thalamus, suggesting a global phenomenon. Investigation of neural microstructure from groups of animals hibernating at different ambient temperatures revealed that there is a linear relationship between neural retraction and minimum body temperature. Despite significant temperature-dependent differences in extent of retraction during torpor, recovery reaches the same final values of cell body area, dendritic arbor complexity, and spine density. This study demonstrates large-scale and seemingly ubiquitous neural plasticity in the ground squirrel brain during torpor. It also defines a temperature-driven model of dramatic neural plasticity, which provides a unique opportunity to explore mechanisms of large-scale regrowth in adult mammals, and the effects of remodeling on learning and memory.

Neurons in hibernating mammals exhibit a dramatic form of plasticity during torpor, with dendritic arbors retracting as body temperature cools and then regrowing rapidly as body temperature rises. In this study, we used immunohistochemical imaging and Western blotting of several presynaptic and postsynaptic proteins to determine the synaptic changes that accompany torpor and to investigate the mechanisms behind these changes. We show torpor-related alterations in synaptic protein localization that occur rapidly and uniformly across several brain regions in a temperature-dependent manner. Entry into torpor is associated with a 50 -65% loss of synapses, as indicated by changes in the extent of colocalization of presynaptic and postsynaptic markers. We also show that the loss of synaptic protein clustering occurring during entry into torpor is not attributable to protein loss. These findings suggest that torpor-related changes in synapses stem from dissociation of proteins from the cytoskeletal active zone and postsynaptic density, creating a reservoir of proteins that can be quickly mobilized for rapid rebuilding of dendritic spines and synapses during the return to euthermia. A mechanism of neural plasticity based on protein dissociation rather than protein breakdown could explain the hibernator's capacity for large, rapid, and repeated microstructural changes, providing a fascinating contrast to neuropathologies that are dominated by protein breakdown and cell death.