Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.

Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.

The journal of neuroscience : the official journal of the Society for Neuroscience.

Background and Purpose—Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment. Methods—We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy. Results—Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recru...

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.31.6.1210

Treatment-Induced Cortical Reorganization After Stroke in Humans

One fundamental function of primary motor cortex (MI) is to control voluntary movements. Recent evidence suggests that this role emerges from distributed networks rather than discrete representations and that in adult mammals these networks are capable of modification. Neuronal recordings and activation patterns revealed with neuroimaging methods have shown considerable plasticity of MI representations and cell properties following pathological or traumatic changes and in relation to everyday experience, including motor-skill learning and cognitive motor actions. The intrinsic horizontal neuronal connections in MI are a strong candidate substrate for map reorganization: They interconnect large regions of MI, they show activity-dependent plasticity, and they modify in association with skill learning. These findings suggest that MI cortex is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning and possibly in cognitive events as well.

https://www.uta.edu/rfmems/Telemetry/Implant%20Sensor/47185_Plasticity%20and%20primary%20motor%20cortex.pdf

Plasticity and primary motor cortex.

In contrast to peripheral nerves, central axons do not regenerate. Partial injuries to the spinal cord, however, are followed by functional recovery. We investigated the anatomical basis of this recovery and found that after incomplete spinal cord injury in rats, transected hindlimb corticospinal tract (CST) axons sprouted into the cervical gray matter to contact short and long propriospinal neurons (PSNs). Over 12 weeks, contacts with long PSNs that bridged the lesion were maintained, whereas contacts with short PSNs that did not bridge the lesion were lost. In turn, long PSNs arborize on lumbar motor neurons, creating a new intraspinal circuit relaying cortical input to its original spinal targets. We confirmed the functionality of this circuit by electrophysiological and behavioral testing before and after CST re-lesion. Retrograde transynaptic tracing confirmed its integrity, and revealed changes of cortical representation. Hence, after incomplete spinal cord injury, spontaneous extensive remodeling occurs, based on axonal sprout formation and removal. Such remodeling may be crucial for rehabilitation in humans.

The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats.

The organization of neocortex in the short-tailed opossum ( Monodelphis domestica ) was explored with multiunit microelectrode recordings from middle layers of cortex. Microelectrode maps were subsequently related to the chemoarchitecture of flattened cortical preparations, sectioned parallel to the cortical surface and processed for either cytochrome oxidase (CO) or NADPH-diaphorase (NADPHd) histochemistry. The recordings revealed the presence of at least two systematic representations of the contralateral body surface located in a continuous strip of cortex running from the rhinal sulcus to the medial wall. The primary somatosensory area (S1) was located medially while secondary somatosensory cortex (S2) formed a laterally located mirror image of S1. Auditory cortex was located in lateral cortex at the caudal border of S2, and some electrode penetrations in this area responded to both auditory and somatosensory stimulation. Auditory cortex was outlined by a dark oval visible in flattened brain sections....

The organization of somatosensory cortex in the short-tailed opossum ( Monodelphis domestica )

Distribution of NADPH-diaphorase cells in visual and somatosensory cortex in four mammalian species.

Publisher Summary This chapter discusses the use of chronically implanted microwire microelectrodes that offers the opportunity to record from large numbers of single neurons and neuron clusters over long periods of time, and from several structures in the sensorimotor system of monkeys. Chronically, implanted arrays of microwires are used to record from neurons in the sensorimotor system of rats. More recently, these procedures have been applied to the somatosensory system of monkeys. Such recording procedures offer advantages over traditional single-unit recording approaches. It is possible to see how neurons in different parts of the system respond to the same events, and determine how the responses of individual neurons relate to each other. The chronically implanted electrodes allow recording under a number of experimental conditions, including recordings in awake animals during behavior. Recordings over weeks to months of time allow studies of how neurons in systems might or might not change in their response characteristics as a result of experience, sensory deprivation, learning, drug treatments, or damage to part of the system. The multi-electrode approach seems to be potentially valuable in studies of both the normal functions of a system, and the plasticity of a system. The chapter present results showing the multielectrode recording from monkeys provide useful and reliable data.

Long-term chronic multichannel recordings from sensorimotor cortex and thalamus of primates.

The orderly representations of sensory surfaces in the brains of adult mammals have the capacity to reor ganize after injuries that deprive these representations of some of their normal sources of activation. Such reorganizations can be produced by injury that occurs peripherally, such as nerve damage or amputation, or after injury to the CNS, such as spinal cord damage or cortical lesion. These changes likely are mediated by a number of different mechanisms, and can be extensive and involve the growth of new connections. Finally, some types of reorganizations may help mediate the recovery of lost functions, whereas others may lead to sensory abnormalities and perceptual errors. NEUROSCIENTIST 3:123-130, 1997

Neeraj Jain

Papers

The organization of somatosensory cortex in the short-tailed opossum ( Monodelphis domestica )

Distribution of NADPH-diaphorase cells in visual and somatosensory cortex in four mammalian species.

Long-term chronic multichannel recordings from sensorimotor cortex and thalamus of primates.

REVIEW ■ : Reorganization of Sensory Systems of Primates after Injury:

The Organization of the Somatosensory System in Primates