Behavioral assessment after spinal cord contusion has long focused on open field locomotion using modifications of a rating scale developed by Tarlov and Klinger (1954). However, on-going modifications by several groups have made interlaboratory comparison of locomotor outcome measures difficult. The purpose of the present study was to develop an efficient, expanded, and unambiguous locomotor rating scale to standardize locomotor outcome measures across laboratories. Adult rats (n = 85) were contused at T7–9 cord level with an electromagnetic or weight drop device. Locomotor behavior was evaluated before injury, on the first or second postoperative day, and then for up to 10 weeks. Scoring categories and attributes were identified, operationally defined, and ranked based on the observed sequence of locomotor recovery patterns. These categories formed the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale. The data indicate that the BBB scale is a valid and predictive measure of locomotor reco...

A Sensitive and Reliable Locomotor Rating Scale for Open Field Testing in Rats

Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity

Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia

Scientists in many different fields have been attracted to the study of habits because of the power habits have over behavior and because they invoke a dichotomy between the conscious, voluntary control over behavior, considered the essence of higher-order deliberative behavioral control, and lower-order behavioral control that is scarcely available to consciousness. A broad spectrum of behavioral routines and rituals can become habitual and stereotyped through learning. Others have a strong innate basis. Repetitive behaviors can also appear as cardinal symptoms in a broad range of neurological and neuropsychiatric illness and in addictive states. This review suggests that many of these behaviors could emerge as a result of experience-dependent plasticity in basal ganglia–based circuits that can influence not only overt behaviors but also cognitive activity. Culturally based rituals may reflect privileged interactions between the basal ganglia and cortically based circuits that influence social, emotional...

Habits, Rituals, and the Evaluative Brain

Distribution of substance P-like immunoreactivity in the central nervous system of the rat—I. Cell bodies and nerve terminals

Localization of the anatomic substrate for anticonvulsant activity mediated by gamma-aminobutyric acid (GABA) was examined using intracerebral injections of GABA agonists. Blockade of tonic hindlimb extension in the maximal electroshock test and blockade of tonic and clonic seizures produced by pentylenetetrazole and bicuculline were obtained by elevating GABA in the ventral midbrain tegmentum. Elevation of GABA in forebrain and hindbrain areas had no effect on convulsant activity. Blockade of tonic and clonic seizures was also obtained after microinjections of the direct GABA receptor agonist, muscimol, into the midbrain. The substantia nigra was identified as the critical midbrain site for GABA-mediated anticonvulsant activity. Local injection of GABA agonists into the midbrain provided seizure protection without a widespread augmentation of GABA-mediated activity throughout the brain and without impairing either alertness or motor function. Synapses in the substantia nigra appear to represent an important control mechanism for inhibiting the propagation of generalized convulsions.

https://science.sciencemag.org/content/sci/218/4578/1237.full.pdf

Substantia nigra: site of anticonvulsant activity mediated by gamma-aminobutyric acid.

Antagonists of gamma-aminobutyric acid (GABA)- or glycine-mediated neurotransmission, muscarinic cholinergic agonists, and excitatory amino acids and their analogues are all considered to be potent chemoconvulsant agents. However, although systemic injections of these agents have been used to create experimental models of generalized epilepsy, there has been no identification of a specific locus at which any of these drugs act to initiate generalized seizures. We recently located a forebrain region from which seizures can be elicited by the GABA antagonist bicuculline, and now report that manipulations of excitatory amino acid transmission and cholinergic transmission can also elicit seizures from this site. Bilateral clonic seizures can be elicited after unilateral application of picomole amounts of bicuculline, kainic acid or carbachol and micromole amounts of glutamate. Local application of the GABA agonist muscimol prevents the appearance of seizures on subsequent microinjection of all convulsant agents examined, whereas local application of the muscarinic antagonist, atropine, only prevents seizures induced by carbachol. This region is therefore a site of action for the epileptogenic effects of neuroactive agents with diverse mechanisms of action; it may also represent a site at which GABA agonists could function therapeutically to control epileptogenesis.

A crucial epileptogenic site in the deep prepiriform cortex

Spinal cord contusion in the rat: Behavioral analysis of functional neurologic impairment

Convulsive seizures in animal models usually involve one or more of the following components: (1) limbic motor seizures, (2) explosive running-bouncing clonic seizures, and (3) tonic extensor seizures. Each of these components depends on specific and experimentally separable anatomic substrates. Limbic motor seizures depend on forebrain structures for their initiation and propagation, with the prepiriform, piriform, and entorhinal cortices playing a prominent role in conjunction with hippocampus, amygdala, substantia innominata, and mediodorsal thalamus. In contrast, seizures involving running-bouncing clonus or tonic extension depend on neural substrates in the brainstem and do not appear to require the integrity of the forebrain for their development or expression. The inferior colliculus is a region from which running-bouncing seizures can be elicited by chemical or electrical stimulation. Tonic extensor seizures depend on the integrity of the nucleus reticularis pontis oralis, but a specific locus responsible for triggering these seizures has yet to be identified. Under conditions of chronic or repeated seizure activity over prolonged time periods, seizures evoked from the hindbrain can recruit forebrain circuits; conversely, repeated stimulation of forebrain limbic circuits (e.g., kindling) can modify susceptibility to brainstem convulsions. These long-term alterations may result from changes in the activity of seizure "gating" pathways, which are circuits that influence seizure susceptibility by modulating the threshold for the initiation and/or propagation of the seizures. In general, these pathways are not part of any core seizure propagation pathway per se. In many cases, the gating substrates are relatively nonselective as to the type of seizure they can influence. In this category, the substantia nigra and its related circuits within the basal ganglia serve a prominent role. In addition, ascending noradrenergic projections have been implicated in the regulation of seizure threshold. Other gating mechanisms involve thalamic circuitry and pathways originating in cerebellum.

Subcortical structures and pathways involved in convulsive seizure generation.

A dopamine-sensitive adenylate cyclase with characteristics similar to those measured in the striatum is present in the rat substantia nigra. Destruction of dopamine cell bodies by intranigral 6-hydroxydopamine application failed to abolish the response of nigral adenylate cyclase to dopamine. In contrast, brain hemitransection between the striatum and substantia nigra, or a more circumscribed lesion of striatonigral pathways, abolished the dopamine stimulation of adenylate cyclase in the substantia nigra. These results suggest that dopamine receptors within the substantia nigra are not located on dopamine cell bodies but are associated with a pathway, containing gamma-aminobutyric acid or substance P, which projects from forebrain structures to the substantia nigra.

https://science.sciencemag.org/content/sci/195/4277/503.full.pdf

Karen Gale

Papers

Substantia nigra: site of anticonvulsant activity mediated by gamma-aminobutyric acid.

A crucial epileptogenic site in the deep prepiriform cortex

Spinal cord contusion in the rat: Behavioral analysis of functional neurologic impairment

Subcortical structures and pathways involved in convulsive seizure generation.

Dopamine-sensitive adenylate cyclase: location in substantia nigra.