Corinna Darian-Smith

Ubiquitous and temperature-dependent neural plasticity in hibernators.

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.

Synaptic Protein Dynamics in Hibernation

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 hibernators capacity for large, rapid, and repeated microstructural changes, providing a fascinating contrast to neuropathologies that are dominated by protein breakdown and cell death.

Comparing thalamocortical and corticothalamic microstructure and spatial reciprocity in the macaque ventral posterolateral nucleus (VPLc) and medial pulvinar

The detailed morphology of thalamocortical (TC) and corticothalamic (CT) pathways connecting the ventral posterolateral nucleus (VPLc) with the primary somatosensory cortex (areas 3b and 1) and the thalamic pulvinar with the posterior parietal cortex (primarily area 7a), was compared. Each pathway processes information relevant to directed reaching tasks, but whereas VPLc receives its major input from the spinal cord and external environment, the primary afferent to the pulvinar is cortical.

Synaptic Plasticity, Neurogenesis, and Functional Recovery after Spinal Cord Injury

Spinal cord injury research has greatly expanded in recent years, but our understanding of the mechanisms that underlie the functional recovery that can occur over the weeks and months following the initial injury, is far from complete. To grasp the scope of the problem, it is important to begin by defining the sensorimotor pathways that might be involved by a spinal injury. This is done in the rodent and nonhuman primate, which are two of the most commonly used animal models in basic and translational spinal injury research. Many of the better known experimentally induced models are then reviewed in terms of the pathways they involve and the reorganization and recovery that have been shown to follow. The better understood neuronal mechanisms mediating such post-injury plasticity, including dendritic spine growth and axonal sprouting, are then examined.

Loss and recovery of voluntary hand movements in the macaque following a cervical dorsal rhizotomy.

The recovery of manual dexterity was analyzed in the macaque following a cervical dorsal root section that abolished cutaneous feedback from selected digits of one hand. Monkeys were trained to retrieve a target object from a clamp using thumb and index finger opposition. Dorsal rootlets containing electrophysiologically identified axons projecting from the thumb and index finger were then cut in two monkeys (Group 1). In four others (Group 2), additional rootlets shown to innervate the middle finger and thenar eminence were also transected. Three performance parameters were analyzed before and following the rhizotomy: 1) percentage of successful retrievals; 2) digital stratagem (the pattern of digit opposition); and 3) contact time (duration of digit contact with the object before its retrieval). During the first postoperative week, hand function was severely impaired in all monkeys. Over the following weeks, Group 1 monkeys recovered the ability to retrieve the object by opposing the index finger and thumb in >80% of trials. Group 2 monkeys also regained some function in the impaired hand: each monkey adopted a stratagem for grasping the target, using digits that were incompletely deafferented. In the terminal experiment, hand representation in the contralateral somatosensory cortex was electrophysiologically mapped to define hand deafferentation and cortical reactivation further. There was a close correspondence between the cortical map and digit use. Our data imply that the recovery of precision grip using the thumb and index finger depends on the survival of afferents innervating these digits, as well as the proliferation of their central terminals. J. Comp. Neurol. 491:27–45, 2005.

Adult neurogenesis in primate and rodent spinal cord: comparing a cervical dorsal rhizotomy with a dorsal column transection.

Neurogenesis has not been shown in the primate spinal cord and the conditions for its induction following spinal injury are not known. In the first part of this study, we report neurogenesis in the cervical spinal dorsal horn in adult monkeys 6–8 weeks after receiving a well‐defined cervical dorsal rhizotomy (DRL). 5‐Bromo‐2‐deoxyuridine (BrdU) was administered 2–4 weeks following the lesion. Cells colabeled with BrdU and five different neuronal markers were observed in the peri‐lesion dorsal horn 4–5 weeks after BrdU injection. Those colabeled with BrdU and neuron‐specific nuclear protein, and BrdU and glial fibrillary acidic protein were quantified in the dorsal horn peri‐lesion region, and the ipsi‐ and contralateral sides were compared. A significantly greater number of BrdU/neuron‐specific nuclear protein‐ and BrdU/glial fibrillary acidic protein‐colabeled cells were found on the lesion side (P < 0.01). These findings led us to hypothesize that neurogenesis can occur within the spinal cord following injury, when the injury does not involve direct trauma to the cord and glial scar formation. This was tested in rats. Neurogenesis and astrocytic proliferation were compared between animals receiving a DRL and those receiving a dorsal column lesion. In DRL rats, neurogenesis was observed in the peri‐lesion dorsal horn. In dorsal column lesion rats, no neurogenesis was observed but astrocytic activation was intense. The rat data support our hypothesis and findings in the monkey, and show that the response is not primate specific. The possibility that new neurons contribute to recovery following DRL now needs further investigation.

Functional changes at periphery and cortex following dorsal root lesions in adult monkeys.

Chronic peripheral nerve injuries produce neural changes at different levels of the somatosensory pathway, but these responses remain poorly defined. We selectively removed cutaneous input from the index finger and thumb in young adult macaque monkeys by lesioning dorsal rootlets to examine both immediate and long-term systemic responses to this deficit. Corresponding digit representations within somatosensory cortex (SI) were initially silenced, but two to seven months later again responded to cutaneous stimulation of the ‘deafferented’ digits. We remapped cutaneous receptive fields (RFs) within adjacent intact dorsal rootlets two to four months after lesioning. RF distributions had greatly expanded, so that rootlets previously innervating adjacent hand regions now responded to stimulation of the index finger and/or thumb. Thus our results demonstrate peripherally mediated central reorganization.

The Environment for Development of the Embryonic Loggerhead Turtle (Caretta caretta) in Queensland

Although it is recognized that a thorough understanding of the biology of incubation is important in the conservation of marine turtles, the difficulties entailed in obtaining measurements of the clutch environment have led to a paucity of data in this area. This paper describes the measurement of gas exchange and temperature from an array of points in the egg chambers of five loggerhead turtles on the beach at Mon Repos, Queensland, Australia. Water table level was also measured in the hatchery in which these turtle eggs were incubating. The result demonstrated a decrease in oxygen and an increase in carbon dioxide partial pressure in these clutches over the latter half of incubation. Small partial pressure differences between measurement points at the periphery of the egg chamber and the egg shaft in relation to the center of the clutches were found for oxygen and carbon dioxide. Temperatures on average in the egg chambers of the control site and the experimental clutches followed the general pattern of the surface temperature and during the summer of 198687 clutch temperatures rose from approximately 26-33 C. Over the latter half of incubation there was an increase in the temperature at the center of the two experimental egg chambers in comparison with the control site. Daily variations in temperature were most evident on the surface with the variations becoming less as one moved towards the lower periphery of the clutch. Further, the water table level fell by 40 cm and followed the general tidal level in the 3-4 d observation periods. A daily periodic rhythm was also evident in the water table level. These data supplement our knowledge regarding the environment of development and demonstrate similar features to those reported in earlier studies.

Parallel pathways mediating manual dexterity in the macaque

Abstract Transmission of information along appropriately structured parallel pathways ensures that a great deal of information can be transferred from the source to the target very quickly, and with great security-essential features of any motor control system. Studies over the last two decades have established that the corticospinal and corticocerebellar pathways mediating manual dexterity in the primate are structurally organized to sustain the parallel transmission of sensorimotor information in multiple pathways. Serial, hierarchical control systems now seem insufficient to regulate voluntary hand movements. To achieve the required coordination, and precision and speed of execution, they must be combined with parallel control systems, which themselves incorporate elaborate feedforward and feedback controls. To illustrate these issues, two aspects of the structural organization of parallel sensorimotor pathways mediating manual dexterity in the macaque are reviewed. First, we examine the structure of the multiple corticospinal neuron subpopulations projecting from different areas of the frontoparietal cortex and how they are modified following hemisection of the cervical spinal cord. The remarkable recovery of hand function following spinal hemisection, despite the absence of any structural ’bridging’ of the interrupted spinal pathways, and the fact that this is accountable in a parallel but not in a purely serial transmission system, are then reviewed. The second aspect of parallel distributed transmission examined is its occurrence within a single population of relay neurons. Our recent structural analysis of the somatic/dendritic organization of rubrospinal neurons in macaque red nucleus is used. The very large dendritic fields of individual neurons, extending over one-third or more of the nucleus, provide a framework for extracting precise somatotopic information from an input population whose axon terminal arbors overlap extensively, and, which, without effective filtering, would provide poor spatial resolution.

Cuneate nucleus reorganization following cervical dorsal rhizotomy in the macaque monkey: Its role in the recovery of manual dexterity

Immediately following a dorsal rhizotomy that removes input from the thumb, index, and middle fingers, the macaque is unable to execute movements that require controlled apposition of these digits. We have previously shown that within the early weeks and months following one of these lesions, there is 1) a re‐emergence of part or all of the cortical hand map; 2) central axonal sprouting of spared primary afferents into the dorsal horn and cuneate nucleus; and 3) substantial although incomplete recovery of hand function (Darian‐Smith [204] J. Comp. Neurol. 470:134–150; Darian‐Smith and Ciferri [2005] J. Comp. Neurol. 491:27–45). In this study we asked: What neuronal reorganization occurs in the cuneate nucleus during this “recovery” period? And, does it contribute to the recovery of manual dexterity? To address these questions, the representation of the hand was electrophysiologically mapped (by unitary receptive field [RF] recordings) in the pars rotunda of the cuneate nucleus at either 1–2 weeks (short term) or 16–32 weeks (long term) post‐rhizotomy. In short‐term monkeys, the region deprived of input from the thumb, index, and middle finger was found to be unresponsive to cutaneous stimulation. However, at 16–32 weeks later, when dexterity had largely recovered, RFs of cuneate neurons could again be mapped within the cuneate nucleus, primarily in a region bordering the deprived zone. We conclude that the cuneate pre‐ and postsynaptic reorganization that occurs following dorsal rhizotomy plays a key role in the recovery of hand function. J. Comp. Neurol. 498:552–565, 2006.