Biomedical subjects

John K Robinson

Publications and source records attributed to John K Robinson.

9 recordsLinked to original sources

PubMed2006

Combined treatment with neurotrophin-3 and LSD facilitates behavioral recovery from double-hemisection spinal injury in neonatal rats.

We explored functional recovery in two spinal cord injury models following a novel combination treatment (NT-3 + LSD). One group of rats received a staggered double hemisection (DH) at postnatal day 2 (P2) of the left hemicord at T11 and the right hemicord at T12. Another group received complete transection (CT) at T11 on P2. A third group was sham operated. Each of these groups was also treated with the drug combination. Drugs were administered intrathecally above the lesion during surgery, and again s.c. at P4, P6, P8, and P10. Intracellular recording in an in vitro spinal cord preparation at P10-P12 in DH rats revealed weak polysynaptic connections to lumbar motoneurons through the injury region, but only in those receiving NT-3 + LSD; NT-3 or LSD alone had no effect. In behavioral experiments, the frequency of rearing in an open field and hindlimb kicks during swimming was assessed every 3-4 days from P9 to P58. Both CT and DH injury severely impaired rearing and hindlimb kicking during swimming. DH rats treated with NT-3 + LSD showed significantly more kicks during swimming than untreated DH or CT rats and treated CT rats beginning as early as P9 and lasting through the duration of testing. Rearing behavior was also improved by treatment but beginning only in the 3rd postnatal week, the time at which it normally develops. Rearing frequency reached sham control levels by P40. Our results suggest this combination treatment may be a promising new strategy for facilitating recovery from moderate spinal cord injury.

Animals↗

PubMed2005

Galanin and perseveration.

Galanin is a 29/30 amino acid neuropeptide that has been shown to impair learning and memory task performance and also have roles in somatosensation, stress responses, sexual behavior, and feeding regulation. However, little is known about galanin involvement in higher cognitive processes, especially executive processes. Perseveration is a classic sign of frontal cortex damage and failure of executive control. Galanin has been shown to disrupt the performance of maze delayed alternation tasks and the operant, spatial delayed nonmatch-to-position (DNMTP) working memory task, tests especially sensitive to perseverative responding. To better understand this potential involvement of galanin in executive control, the present study tested the hypothesis that galanin induces perseveration. The first experiment examined the effects of galanin (10, 20 microg i.c.v.) on the performance of a simple operant response alternation task in which stimuli were assigned to one of two spatially distinct locations to produce extended sequences of presentations to one location, separated by a 10-s intertrial interval. The second experiment looked at the effects of galanin (5, 20 microg i.c.v.) on the performance of non-delayed match-to-position and nonmatch-to-position conditional discrimination operant tasks in which a minimal 1.0 s time interval separated responses. Finally, the effects of galanin (10, 20 microg i.c.v.) on delayed match-to-position (DMTP) performance were examined to determine whether response alternation (i.e., nonmatching) was critical to observing a galanin-induced impairment in this task. Galanin reduced the rate of trial completion in all the tasks, but did not alter simple or conditional discrimination accuracy. Galanin (10 microg) impaired DMTP performance in a delay-independent manner. Together, these data suggest that galanin does not produce perseveration, but are consistent with a galanin-induced decrease in reinforcer strength.

Animals↗

PubMed2005

Construct validity of an operant signal detection task for rats.

Many psychoactive drugs produce simultaneous effects on a variety of psychological processes. Behavioral measures in tasks designed to assess cognitive processes in rodents should be able to characterize and dissociate these multiple influences. The present study evaluated how error measures in a classic two-choice operant spatial signal detection paradigm were affected by procedural manipulations of the motivational state of the rat, stimulus properties, and alterations of the inter-trial interval. The experiments were conducted in a two lever operant chamber in which a cue lamp was mounted over each lever. The rats were trained to respond quickly to a short illumination of one of the cue lamps at one of three durations (100, 300 or 1000 ms), presented in a random order. The procedural manipulations were (1) to allow pre-session water access to the normally water-restricted subjects, (2) to vary the intertrial interval (ITI) between sessions, (3) to reduce the intensity of the discriminative stimuli, and (4) to manipulate the variability of the ITI within a session. Stimulus duration-dependent decreases of detection accuracy were observed following pre-session water access and when the intertrial interval was decreased. A reduction of stimulus intensity resulted in decreased accuracy at all stimulus durations. Varying the ITI within the session produced stimulus duration-independent alterations of detection accuracy but no change in the frequency of errors of omission. These findings show that distinct patterns of performance deficits result from manipulating different components of this task and that errors of omission and commission often co-vary and raise questions about the definitions of vigilance and sustained attention as these constructs apply to signal detection tasks that present spatially distinct stimuli.

Animals↗

PubMed2005

Assessment of new functional roles for galanin in the CNS.

There is considerable evidence that galanin plays an important role in food intake, nociception, stress reactivity, sexual behavior, and learning. However, its involvement in other important behavioral processes, especially higher cognition, has not been systematically investigated. This review summarizes our recent efforts to explore the role of galanin in executive processes as well as in fundamental motivational and motor productive processes that are essential to the behavioral assessment of cognitive constructs in rodents. Our work points to a role in reward processes and physiological water balance regulation, and argues against a role for galanin in fine motor production and maintenance, simple visual discrimination, and perseveration.

Animals↗

PubMed2005

Intracerebroventricular administration of galanin decreases free water intake and operant water reinforcer efficacy in water-restricted rats.

The 29/30 amino acid neuropeptide galanin coexists with vasopressin in the hypothalamus and has been shown to inhibit the actions of vasopressin and aldosterone, suggesting an inhibitory role for galanin in physiological water retention mechanisms and water seeking and water consumption behavior. Little work, however, has examined a role for galanin in water intake regulation. Furthermore, many experiments that have reported galanin-induced impairments in the performance of tasks thought to measure learning and memory have used water restriction routines and water reinforcers to maintain responding. Therefore, the present study examined the effects of intracerebroventricularly administered galanin (5.0-20.0 microg/5 microl) on free water consumption during a 10 min test session and a follow up open field exploration, an operant progressive ratio (PR) schedule, a test used to assess reinforcer strength, and an operant fixed time schedule (FT 20) in 23.5h water restricted rats. Finally, in an additional experiment that was designed to simulate the effects of a galanin-induced decrease in water reinforcer efficacy, the rats were allowed access to water prior to testing in an operant delayed non-matching to position (DNMTP) task. A galanin-induced decrease in water consumption was observed in both the free access test and the FT 20 at the 20 microg dose, but no significant galanin-induced alterations in open field behavior. A decrease in responses emitted and rewards received was observed on the PR schedule at the 5, 10, and 20 microg doses. Pre-session access to water significantly reduced the number of trials per session in the DNMTP but did not reduce accuracy. This study is the first to observe a galanin-induced reduction in water intake and reinforced operant behavior, and suggests that galanin may play a role in regulating water intake and reinforcement. However, the present data also suggest that DNMTP choice accuracy deficits observed previously cannot be attributed to a galanin-induced change in reinforcer efficacy.

Animals↗

PubMed2004

CD36 expression and brain function: does CD36 deficiency impact learning ability?

This article first presents an overview of published literature documenting the role of the scavenger receptor CD36 in activation of brain microglia with reference to brain pathologies such as Alzheimer's and malaria. Second, the possibility that CD36 may play a role in brain FA metabolism is discussed. Long-chain polyunsaturated fatty acids (PUFAs) are important for brain function and are mostly derived from the plasma. Based on its role in facilitating FA uptake in several tissues and cell types, CD36 expressed on microvascular endothelial cells in the brain may facilitate local uptake of PUFAs. Alternatively, CD36 may influence brain FA supply indirectly via impacting utilization of dietary FA or their metabolism in tissues such as the liver. We examined the possibility that CD36 expression impacts brain function by evaluating the behavior of CD36 null mice using a battery of standard tests. Our data indicate that CD36 deficient mice have normal patterns of activity, anxiety and exploration of novel environments. However they appear to have a significant impairment in learning ability. These findings could provide a new perspective regarding the regulation of brain lipid metabolism.

Animals↗

PubMed2004

Intracerebroventricularly administered galanin does not alter operant reaction time or differentially reinforced high rate schedule operant responding in rats.

Galanin (Gal) is a 29/30 amino acid neuroendocrine peptide that impairs learning and memory processes, stimulates feeding, and modulates somatosensory, sex, and stress responses. Anatomical markers for Gal are found throughout the brain, including in the caudate-putamen and substantia nigra motor regions. Many of the behavioral tests that have been used to study the involvement of Gal in complex behavioral processes are motorically demanding, but no research has specifically investigated the involvement of Gal in response initiation or the maintenance of fine motor action. Therefore, the present study examined the effects of intraventricularly administered Gal on two highly sensitive operant tasks designed to detect alteration of these response properties. Response initiation was studied using a light-dark discrimination reaction time task that required a correct response within 2.5s of a spatially and temporally uncertain stimulus onset. The ability to perform high local rates of responding was studied using an operant differential reinforcement of high rate (DRH) of responding task. Gal (10-20 microg, i.c.v.) did not alter reaction time or inter-response time distributions in either task, though did substantially reduce the total number of responses and reinforcers obtained on the DRH schedule. These results are consistent with a Gal-induced reduction of reinforcer efficacy rather than Gal-disruption of response initiation or response patterning.

Analysis of Variance↗

PubMed2004

Regulation of feeding by galnon.

Galanin is a neuropeptide that has been implicated in multiple bioactivities, inter alia eating disorders. In this study, we have examined the effects of galnon, a novel low molecular weight galanin receptor ligand. Previous studies have shown that galnon acts as a systemically active, blood-brain barrier crossing agonist on galanin signaling both in vitro and in vivo, inhibiting pentylenetetrazole-induced seizures. Here, intracerebroventricular (10-20 microg) and intraperitoneal (1.5-5 mg/kg) administration of galnon induced a strong, dose-dependent reduction of food intake in rats and mice. This reduction in feeding occurred without reducing general activity and was shown to be attenuated by an intracerebroventricular administration of M35, a peptide galanin antagonist. These data demonstrate that galnon is a promising tool for studies of the involvement of galanin in feeding disorders and other behavioral processes.

Animals↗

PubMed2004

Galanin and cognition.

Since the neuropeptide galanin's discovery in 1983, information has accumulated that implicates it in a wide range of functions, including pain sensation, stress responses, appetite regulation, and learning and memory. This article reviews the evidence for specific functions of galanin in cognitive processes. Consistencies as well as gaps in the literature are organized around basic questions of methodology and theory. This review shows that although regularities are evident in the observed behavioral effects of galanin across several methods for measuring learning and memory, generalization from these findings is tempered with concerns about confounds and a restricted range of testing conditions. Furthermore, it is revealed that many noncognitive behavioral constructs that are relevant for assessing potential roles for galanin in cognition have not been thoroughly examined. The review concludes by laying out how future theory and experimental work can overcome these concerns and confidently define the nature of the association of galanin with particular cognitive constructs.

Behavior↗