Tammy L. Ivanco

Skilled forelimb movements in prey catching and in reaching by rats (Rattus norvegicus) and opossums (Monodelphis domestica): relations to anatomical differences in motor systems

Traditional anatomical/behavioral classifications suggest that rats and opossums have simple motor systems and are impoverished with respect to their ability to make prehensile movements. Nevertheless, the motor system in rats and opossums represent extremes in relative size and complexity suggesting that a behavioral analysis of the movement competencies of these species will provide insights into the significance of such anatomical differences. This paper examines the movements that the two species use in catching crickets and in reaching for food items. Both species could use a single limb to reach out and grasp prey during prey catching and both could use a single limb to take food from a shelf. Both species could transport the food to the mouth by using a single paw. The food handling behavior of the rats was more complex than that of the opossums, however. They used a variety of prey catching movements and extensively manipulated the prey to remove the legs and wings before eating only the head and body. Additionally the rats made rotatory limb movements of aiming, pronation, and supination, when reaching. For both cricket catching and reaching, they used their digits more than did the opossums. The suggestion also emerged from the results that the movements of the opossums were more fixed and species-typical whereas those of the rats were more plastic and individualistic. Thus, the skilled movements of both species are more complex than is generally recognized and the greater complexity of the rat movements parallels their more complex motor system. These results are discussed in relation to anatomical differences in the motor system and, specifically, to differences in the terminal fields of the pyramidal tract. It is concluded that the motor abilities of nonprimate mammals have been vastly underrated.

Physiological consequences of morphologically detectable synaptic plasticity: potential uses for examining recovery following damage.

A growing literature indicates that brain structure is modified in various ways with experience. In this paper we briefly survey evidence that the brain retains the capacity to modify its organization in response to demands, including demands resulting from learning, throughout the lifetime. We attempt to address whether these experience-induced changes are accompanied by physiological changes that indicate a functional reorganization of the brain. The kinds of morphological changes that have been observed following brain injury appear to be very similar to those seen after learning. The similarity suggests that many of the basic mechanisms of synaptic change in the brain may be utilized for both functions. This suggests that we can take advantage of some of the methods used to test the changes in physiology with behavioral manipulations to examine the damaged brain. We advocate utilizing electrophysiological techniques to measure functional recovery from brain injury as these may be useful in evaluating both spontaneous recovery from damage and the therapeutic benefits of training, or other therapies.

Vascular-specific growth factor angiopoietin 1 is involved in the organization of neuronal processes

Neuronal processes and vessels have similar branching and bifurcation patterning in the adult body and appear to use many of the same molecules during their development, including vascular endothelial growth factor, Notch, neuropilin, and ephrins/Ephs. We were interested in determining whether the endothelial growth factor angiopoietin (Ang) has a unique role in the nervous system in addition to its angiogenic role. By using a mouse molecular genetics approach, we overexpressed Ang1 in the mouse forebrain and observed increases in overall vascularization, consistent with prior reports describing the role of Ang1. Nonvascular events, involving alterations in the dendritic organization of layer II motor cortex neurons, dentate granule cells, and pyramidal cells of CA1, were seen, suggesting that Ang1 was able to influence the growth of these processes. The angiopoietin tyrosine kinase receptor Tie2 was not found on neurons or their processes, but β1 integrin was and has previously been found to act as an Ang receptor. Our findings provide some of the first data evaluating the interactions between the developing nervous system and the vascular protein Ang1. Understanding interactions between the developing nervous and vascular systems will lead to novel insight into how the two systems interact throughout development, during senescence, and in disease. J. Comp. Neurol. 482:244–256, 2005.

Morphology of layer III pyramidal neurons is altered following induction of LTP in sensorimotor cortex of the freely moving rat

The organization of specific cortical connections can be altered by sensory and motor experience. These changes are believed to result from activity‐dependent changes in synaptic connectivity, similar to those induced in the hippocampus by high‐frequency stimulation in long‐term potentiation (LTP) experiments. If similar mechanisms are involved, then neocortical LTP induction may induce some of the same morphological changes that are seen following learning. We induced LTP in the contralateral sensorimotor cortex by repeated, daily tetanization of the corpus callosum in chronically implanted, freely moving rats. Anatomical results showed that the LTP induction was associated with alterations in dendrite morphology and increased spine density. These changes are qualitatively and quantitatively similar to those commonly observed in studies in which rats are housed in complex environments. The similarity of results following exposure to complex environments and after LTP induction in the neocortex may indicate a reliance on the same cellular mechanisms in both situations. Synapse 37:16–22, 2000.

MAP2 and synaptophysin protein expression following motor learning suggests dynamic regulation and distinct alterations coinciding with synaptogenesis.

Learning a new motor skill can induce neuronal plasticity in rats. Within motor cortex, learning-induced plasticity includes dendritic reorganization, synaptogenesis, and changes in synapse morphology. Behavioral studies have demonstrated that learning requires protein synthesis. It is likely that some of the proteins synthesized during learning are involved in, or the result of, learning-induced structural plasticity. We predicted the expression of proteins involved in neural plasticity would be altered in a learning dependent fashion. Long-Evans rats were trained on a series of motor tasks that varied in complexity, so that the effects of activity could be teased apart from the effects of learning. The motor cortices were examined for MAP2 and synaptophysin protein using Western blotting and immunohistochemistry. Western blotting revealed that expression of MAP2 was not detectably influenced by learning, whereas synaptophysin expression increased on day 1, 3, and 5 of complex motor skill learning. Expression of MAP2 does not seem to indicate difficulty of task or duration of training time, whereas increases in synaptophysin expression, which appear diffusely across the cortex, seem to be correlated with the first 5 days of motor skill learning. Similar findings with GAP-43 suggest the change in synaptophysin may coincide with synapse formation. Immunohistochemistry did not reveal any localized changes in protein expression. These data indicate a difference in learning-induced expression in the mammalian brain compared to reports in the literature, which have often focused on stimulation to induce alterations in protein expression.

Persistent motor deficit following infusion of autologous blood into the periventricular region of neonatal rats

Periventricular hemorrhage (PVH) in the brain of premature infants is often associated with developmental delay and persistent motor deficits. Our goal is to develop a rodent model that mimics the behavioral phenotype. We hypothesized that autologous blood infusion into the periventricular germinal matrix region of neonatal rats would lead to immediate and long-term behavioral changes. Tail blood or saline was infused into the periventricular region of 1-day-old rats. Magnetic resonance (MR) imaging was used to demonstrate the hematoma. Rats with blood infusion, as well as saline and intact controls, underwent behavior tests until 10 weeks age. Blood-infused rats displayed significant delay in motor development (ambulation, righting response, and negative geotaxis) to 22 days of age. As young adults, they exhibited impaired ability to stay on a rotating rod and to reach for food pellets. MR imaging at 10 weeks demonstrated subsets of rats with normal appearing brains, focal cortical infarcts, or mild hydrocephalus. There was a good correlation between MR imaging and histological findings. Some rats exhibited periventricular heterotopia and/or subtle striatal abnormalities not apparent on MR images. We conclude that autologous blood infusion into the brain of neonatal rats successfully models some aspects of periventricular hemorrhage that occurs after premature birth in humans.

Anesthetized Long Evans rats show similar protein expression and long-term potentiation as Fischer 344 rats but reduced short-term potentiation in motor cortex

A number of studies describe strain-related differences in the motor behavior of rats. Inbred albino F344 rats are found to be impaired in procedural spatial learning, skilled reaching, and over ground locomotion in relation to pigmented out bred Long Evans (LE) rats. These deficits could be related to the functional differences in the motor cortex of the two strains, and the objective of the present study was to examine this hypothesis. Synaptic transmission was examined in the two rat strains, using long-term potentiation (LTP) and short-term potentiation (STP), two electrophysiological measures of neural function and learning. Field potentials were evoked in the motor cortex of anesthetized Long Evans and Fischer 344 (F344) rats in response to contralateral white matter stimulation. The main findings indicated that (1) baseline-evoked responses in the two strains was similar, indicating similar basal levels of synaptic strength, (2) LTP was induced in both strains of rats, suggesting similar synaptic efficacy in the two strains of rats, and (3) STP was enhanced in the Fischer 344 rats, suggesting differences in synaptic function. Protein expression also revealed that the two strains did not differ with respect to structural or synaptic protein expression. Thus, the two strains exhibit motor skill differences despite a great degree of physiological similarity in motor cortex. The results are discussed in relation to the greater utility of using the Long Evans rat for examining the neural basis of plasticity and models of disease, especially if motor tasks are evaluated.

Acute Administration of Interleukin-1β Disrupts Motor Learning

Proinflammatory cytokines have been shown to disrupt the normal transfer of short-term memory to long-term storage sites. Previous research has focused predominantly on the effect of cytokines on hippocampus-mediated spatial learning. To further understand the effects of cytokines on learning and memory, the authors evaluated the effects of interleukin-1beta (IL-1beta) on a motor learning task. Male Long-Evans rats were rewarded with food pellets after they traversed a runway. The runway was either flat (control condition) or had up-ended dowels (motor learning condition). Subjects traversed the flat runway or dowel task for 5 days, 10 trials per day, and were treated with either saline or with 4 microg/kg IL-1beta immediately after training on the first 2 days. Rats in the motor learning task treated with IL-1beta were consistently slower at traversing the runway. IL-1beta did not impair performance in the control condition; rats in the flat condition performed similarly regardless of whether they were treated with saline or IL-1beta. These data are the first evidence demonstrating IL-1beta can disrupt performance in a motor learning task.

Changes in dendritic morphology and spine density in motor cortex of the adult rat after stroke during infancy.

Cognitive and motor deficits are pervasive in children that suffer early brain injury. The aim of this study was to determine the impact that early damage has on dendritic spine density and other aspects of dendritic morphology of neurons in the motor cortex. Also of interest was how changes in dendritic structure evolved across the lifespan. Ischemia was induced in 10‐day‐old Long Evans rats by injection of Rose Bengal dye and a laser positioned over right motor cortex. Animals were sacrificed at two and six months of age, and brains were processed for Golgi‐Cox staining. Animals exposed to early damage exhibited increases in length of basilar dendrites at two months of age, however no differences in spine density were found across groups at this age. At six months of age, injured animals demonstrated an overall decrease in apical and basilar spine density. Our results suggest that the changes in dendritic length and spine density observed after early damage are unable to be maintained as the animal ages. The observation that increases in spine density do not necessarily coincide with increases in dendritic length suggests that the two processes may not be dependent on one another and suggest two independent plasticity processes responding to damage. Synapse 2010.

BDNF expression increases without changes in play behavior following concussion in juvenile rats (Rattus Norvegicus): brief report

ABSTRACT Purpose: Young children have a high risk of concussion or mild traumatic brain injury (mTBI). Children often appear healthy soon after mTBI, but some have pervasive cognitive and/or motor impairments. Understanding underlying mechanisms recruited after concussion may help for return to play protocols and mitigating what might be lifelong impairments. Methods: We investigated molecular and behavioral changes in a rat model of childhood concussion. Rats received an injury or sham procedure at an age approximately equivalent to the human period of early childhood. Social play was analyzed for behavioral differences. Tissue from the right motor cortex (impacted), left motor cortex, and medial prefrontal cortex were analyzed for brain derived neurotrophic factor (BDNF) protein. Results: Play behavior was not significantly different between conditions. BDNF levels were much higher in both the right and left motor cortices of the mTBI group compared to medial prefrontal cortex, which is relatively remote from the impact site, within the mTBI group and all tissue collected from the sham group. Conclusions: There is ongoing plastic change at the cellular level in both the impacted area and the well-connected contralateral area after a concussion, suggesting compensatory mechanisms after injury are still at play.