Neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian organisms, including humans. Neural stem cells can also be derived from more primitive embryonic stem cells. The location of the adult stem cells and the brain regions to which their progeny migrate in order to differentiate remain unresolved, although the number of viable locations is limited in the adult. The mechanisms that regulate endogenous stem cells are poorly understood. Potential uses of stem cells in repair include transplantation to repair missing cells and the activation of endogenous cells to provide "self-repair. " Before the full potential of neural stem cells can be realized, we need to learn what controls their proliferation, as well as the various pathways of differentiation available to their daughter cells.

https://science.sciencemag.org/content/sci/287/5457/1433.full.pdf

Mammalian neural stem cells.

Neuronal plasticity is a central theme of modern neurobiology, from cellular and molecular mechanisms of synapse formation in Drosophila to behavioural recovery from strokes in elderly humans. Although the methods used to measure plastic responses differ, the stimuli required to elicit plasticity are thought to be activity-dependent. In this article, we focus on the neuronal changes that occur in response to complex stimulation by an enriched environment. We emphasize the behavioural and neurobiological consequences of specific elements of enrichment, especially exercise and learning.

Neural consequences of environmental enrichment.

Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.

Learning and memory functions of the Basal Ganglia.

In animal models, immature neural precursors can replace lost neurons, restore function and promote brain self-repair. Clinical trials in Parkinson's disease suggest that similar approaches may also work in the diseased human brain. But how realistic is it that cell replacement can be developed into effective clinical therapy?

Cell replacement therapies for central nervous system disorders.

Multiple parallel memory systems in the brain of the rat.

Rats were trained in a specially designed, multichoice operant chamber on a visual choice reaction time task designed to assess performance on each side of the rat’s body. The task required animals to sustain a nose poke in a central hole, until a brief light stimulus was presented in either of two holes that were located on the same side of the box. Once the rats were trained to perform the task to both sides independently they received unilateral injections of quinolinic acid into the dorsal striatum.

Postoperatively, lesioned animals were impaired when performing the task on the side contralateral to the lesion. The time taken to initiate contralateral responses was increased. Contralateral responses were also exclusively biased toward the nearer of the two response locations, regardless of the location of the stimulus. This was interpreted as a specific impairment in generating responses in contralateral space. In contrast, no comparable deficit was seen when the animals performed the task on the side ipsilateral to the lesion. Additional postoperative challenges, in which response options were presented bilaterally, showed this response deficit to be defined in egocentric coordinates, with the severest response deficits for the most contralateral locations.

https://www.jneurosci.org/content/jneuro/17/22/8919.full.pdf

Unilateral lesions of the dorsal striatum in rats disrupt responding in egocentric space

Medial prefrontal and neostriatal lesions disrupt performance in an operant delayed alternation task in rats.

Striatal lesions disrupt both motor and cognitive performance in rats, many aspects of which can be restored by striatal transplants. Because the normal striatum is involved in the formation and maintenance of motor habits, it has been hypothesized that grafted animals may require explicit retraining to relearn previously established habits that have been disrupted by the lesions. We have used a lateralized-discrimination task to reproduce this “learning to use the transplant” effect, combined with a transfer-of-training paradigm to demonstrate that recovery requires relearning specific lateralized stimulus–response associations and cannot be explained simply by a generalized training-dependent improvement in motor skill. These results have clear implications for developing appropriate strategies for the rehabilitation of Huntington’s disease patients participating in clinical transplantation programs.

Peter J. Brasted

Papers

Unilateral lesions of the dorsal striatum in rats disrupt responding in egocentric space

Medial prefrontal and neostriatal lesions disrupt performance in an operant delayed alternation task in rats.

Associative plasticity in striatal transplants

Striatal lesions produce distinctive impairments in reaction time performance in two different operant chambers

Embryonic donor age and dissection influences striatal graft development and functional integration in a rodent model of Huntington's disease.