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Biomedical subjects

Paul E Gold

Publications and source records attributed to Paul E Gold.

At least 19 recordsLinked to original sources
PubMed2006

Microdialysis measures of functional increases in ACh release in the hippocampus with and without inclusion of acetylcholinesterase inhibitors in the perfusate.

Because brain extracellular acetylcholine (ACh) levels are near detection limits in microdialysis samples, an acetylcholinesterase (AChE) inhibitor such as neostigmine is often added to microdialysis perfusates to increase ACh levels in the dialysate, a practice that raises concerns that the inhibitor might alter the results. Two experiments compared functional differences in ACh release with and without neostigmine. In the first experiment, 30-60% increases in extracellular ACh concentrations in the hippocampus were evident during food-rewarded T-maze training with 20-500 nm neostigmine in the perfusate but no increases were seen without neostigmine. In the second experiment, 78% increases in ACh release in the hippocampus were seen after injections of the GABA(A) receptor antagonist, bicuculline, into medial septum only if neostigmine (50 nm) was included in the perfusate. These findings suggest that, in the hippocampus, endogenous brain AChEs are very efficient at removing extracellular ACh, obscuring differences in ACh release in these experiments. Therefore, inclusion of AChE inhibitors in the microdialysis perfusate may be necessary under some conditions for observations of functional changes in release of ACh in the hippocampus.

Acetylcholine↗
PubMed2005

Modulation of memory with septal injections of morphine and glucose: effects on extracellular glucose levels in the hippocampus.

The concentration of glucose in the extracellular fluid (ECF) of the hippocampus decreases substantially during memory testing on a hippocampus-dependent memory task. Administration of exogenous glucose, which enhances task performance, prevents this decrease, suggesting a relationship between hippocampal glucose availability and memory performance. In the present experiment, spontaneous alternation performance and task-related changes in hippocampal ECF glucose were assessed in rats after intraseptal administration of morphine, which impairs memory on a spontaneous alternation task, and after co-administration of intraseptal glucose, which attenuates that impairment. Consistent with previous findings, spontaneous alternation testing resulted in a decrease in hippocampal ECF glucose levels in control rats. However, rats that received intraseptal morphine prior to testing showed memory impairments and an absence of the task-related decrease in hippocampal ECF glucose levels. Intraseptal co-administration of glucose with morphine attenuated the memory impairment, and ECF glucose levels in the hippocampus decreased in a manner comparable to that seen in control rats. These data suggest that fluctuations in hippocampal ECF glucose levels may be a marker of mnemonic processing and support the view that decreases in extracellular glucose during memory testing reflect increased glucose demand during memory processing.

Analgesics, Opioid↗
PubMed2005

Effects of injections of glucose into the dorsal striatum on learning of place and response mazes.

The present experiment tested the hypothesis that facilitation of striatal function with intra-striatal glucose injections would facilitate learning a striatum-dependent response maze and impair learning a hippocampus-dependent place maze. Food-deprived Sprague-Dawley male rats were trained to find food in a Y-maze. In the place version of the maze, rats were rewarded for learning to go to an arm located in a fixed location while in the response task rats were rewarded for consistently turning in the same direction at the choice point. Artificial cerebrospinal fluid (1 microL) containing either 0.7 nmol of glucose (control) or 20 nmol of glucose was injected bilaterally into the dorsal striatum immediately before training. The animals were trained to a criterion of 9/10 correct choices. In the place maze, glucose injections impaired learning, as measured by number of trials required to reach 9/10 correct. However, in the response task, glucose injections did not enhance learning. A subsequent experiment examined the effects of intra-striatal glucose injections on acquisition of the response task under two different visual cue conditions, addition of an intra-maze light cue that predicted the correct arm or with removal of most visual extramaze cues. Glucose again failed to facilitate acquisition of the response task under these conditions. These findings suggest that facilitation of striatal function via intra-striatal glucose injections is sufficient to impair place learning but not to enhance response learning, perhaps separating the neurochemical mechanisms for striatal involvement in impairment of place and enhancement of response learning.

Animals↗
PubMed2005

Glucose and age-related changes in memory.

Epinephrine, released from the adrenal medulla, enhances memory in young rats and mice and apparently does so, at least in part, by increasing blood glucose levels. Like epinephrine, administration of glucose enhances cognitive functions in humans and rodents, including reversing age-related impairments in learning and memory. Epinephrine responses to training are increased in aged rats but the subsequent increase in blood glucose levels is severely blunted. The absence of increases in blood glucose levels during training might contribute to age-related deficits in learning and memory. Also, extracellular glucose levels in the hippocampus are depleted during spontaneous alternation testing to a far greater extent in aged than in young rats. Importantly, systemic injections of glucose block the depletion in the hippocampus and also enhance performance on the alternation task. Thus, the extensive depletion of extracellular glucose during training in aged rats may be associated with age-related memory impairments, an effect that might be related to - or may exacerbate - the effects on learning and memory of an absence of the increases in blood glucose levels to training as seen in young rats. Together, these findings suggest that age-related changes in both peripheral and central glucose physiology contribute to age-related impairments in memory.

Age Factors↗
PubMed2005

Glucose injections into the dorsal hippocampus or dorsolateral striatum of rats prior to T-maze training: modulation of learning rates and strategy selection.

The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial (P(crit)) administered after rats achieved criterion (nine of 10 correct choices) varied by group. All groups predominately exhibited a response strategy on a probe trial administered after overtraining, i.e., after 90 trials. In experiment 1, rats that received intrahippocampal glucose injections showed enhanced acquisition of the T-maze and showed increased use of response solutions at P(crit) compared with that of unimplanted and artificial cerebral spinal fluid (aCSF)-treated groups. These findings suggest that glucose enhanced hippocampal functions to accelerate the rate of learning and the early adoption of a response strategy. In experiment 2, rats that received intrastriatal glucose injections exhibited place solutions early in training and reached criterion more slowly than did aCSF controls, with learning rates comparable to those of unoperated and operated-uninjected controls. Relative to unoperated, operated-uninjected and glucose-injected rats, rats that received intrastriatal aCSF injections showed enhanced acquisition of the T-maze and increased use of response solutions at P(crit). The unexpected enhanced acquisition seen after striatal aCSF injections suggests at least two possible interpretations: (1) aCSF impaired striatal function, thereby releasing competition with the hippocampus and ceding control over learning to the hippocampus during early training trials; and (2) aCSF enhanced striatal functioning to facilitate striatal-sensitive learning. With either interpretation, the results indicate that intrastriatal glucose injections compensated for the aCSF-induced effect. Finally, enhanced acquisition regardless of treatment was accompanied by rapid adoption of a response solution for the T-maze.

Animals↗
PubMed2005

Glucose regulation of memory for reward reduction in young and aged rats.

Although baseline blood glucose levels in aged Fischer-344 rats are comparable to those of young rats, the rise in blood glucose in response to training-related stress is substantially attenuated. The diminished response may contribute to increased depletion of extracellular brain glucose levels during training in aged rats; the depletion is blocked and memory is enhanced by systemic injections of glucose. The present experiment examined the role of glucose in regulating memory for reward reduction training. Blood glucose levels exhibited a significant rise after reward reduction trials in young adult but not 2-year-old rats. Although young and aged rats exhibited comparable learning during the day of reward reduction training, aged rats exhibited more rapid forgetting of the learning response. Post-training glucose injections (200 mg/kg, i.p.) facilitated memory formation and slowed the rate of forgetting in young and old rats, consistent with the view that deficiencies in circulating glucose responses to training may contribute to the rapid forgetting evident in aged Fischer-344 rats.

Aging↗
PubMed2005

Acetylcholine release in hippocampus and striatum during testing on a rewarded spontaneous alternation task.

The present experiment tested male Sprague-Dawley rats for spontaneous alternation performance in a food-rewarded Y-shaped maze. Microdialysis samples, later assessed for acetylcholine concentration, were collected from the hippocampus and striatum of each rat prior to and during testing; testing sessions lasted 20 min. Early in testing, rats alternated at a rate of 72%. Alternation scores increased throughout the 20-min testing session and reached 93% during the last 5 min. The behavioral findings suggest that, during testing, rats changed the basis for their performance from a spatial working memory strategy to a persistent turning strategy. ACh release in both hippocampus and striatum increased at the onset of testing. Increases in ACh release in the striatum began at 18% above baseline during the first 5 min of testing and steadily increased reaching 58% above baseline during the final 5 min. The progressive rise of striatum ACh release during testing occurred at about the time rats adopted a persistent turning strategy. In contrast, ACh release in the hippocampus increased by 50% with the onset of testing and remained at this level until declining slightly during the last 5 min of testing. The relative changes in ACh release in the striatum and hippocampus resulted in a close negative relationship between the ratio of ACh release in the hippocampus/striatum and alternation scores.

Acetylcholine↗
PubMed2004

Increases in extracellular fluid glucose levels in the rat hippocampus following an anesthetic dose of pentobarbital or ketamine-xylazine: an in vivo microdialysis study.

Using in vivo microdialysis, we examined glucose levels in the extracellular fluid (ECF) of the hippocampus and in the blood prior to and during pentobarbital (45 mg/kg) or ketamine-xylazine (66 mg/kg, 7 mg/kg) anesthesia. Anesthesia with either pentobarbital or ketamine-xylazine significantly increased hippocampal ECF glucose levels (mean peak increases of +71% and +85%, respectively). In addition, there were substantial increases in blood glucose levels (mean peak increases of +24% and +30%, respectively). The increased levels of hippocampal ECF glucose during anesthesia complement past evidence for decreases in ECF glucose in the hippocampus observed while rats perform a memory task sensitive to hippocampal damage, providing further support for the view that ECF glucose levels in the hippocampus are dynamically coupled to local neural activity.

Analgesics↗
PubMed2004

Impaired and spared cholinergic functions in the hippocampus after lesions of the medial septum/vertical limb of the diagonal band with 192 IgG-saporin.

To lesion the cholinergic input to the hippocampus, rats received injections of 192 IgG-saporin into the medial septum/vertical limb of the diagonal band (MS/VDB). The lesions produced near-total loss of choline acetyltransferase (ChAT)-positive neurons in the MS/VDB. The loss was accompanied, however, by only partial decreases (to 40% of control levels) in acetylcholine (ACh) release in the hippocampus. Moreover, ACh release in the hippocampus increased when lesioned and control rats were tested on a spontaneous alternation task, indicating that there was significant residual cholinergic function in the hippocampus. The lesions were sufficient to impair spontaneous alternation scores. However, this impairment could be reversed by either systemic or intra-hippocampal injections of the indirect cholinergic agonist, physostigmine, providing additional evidence of residual and effective cholinergic functions in the hippocampus of lesioned rats. Moreover, systemic injections of physostigmine at doses that produced mild tremors in control rats led to more severe tremors in the lesioned rats, suggesting upregulation of cholinergic mechanisms after saporin lesions, likely in brain areas other than the hippocampus. Thus, these findings provide evidence for decreases in cholinergic input to the hippocampus accompanied by deficits on a spontaneous alternation tasks. The findings also provide evidence for considerable residual cholinergic input to the hippocampus after saporin lesions of the MS/VDB. Together, the results suggest that 192 IgG-saporin lesions of the MS/VDB, using methods often employed, do not fully remove septohippocampal cholinergic input to the hippocampus but are nonetheless sufficient to produce impairments on a task impaired by hippocampal lesions.

Acetylcholine↗
PubMed2004

Coordination of multiple memory systems.

On the basis of lesions of different brain areas, several neural systems appear to be important for processing information regarding different types of learning and memory. This paper examines the development of pharmacological and neurochemical approaches to multiple memory systems from past studies of modulation of memory formation. The findings suggest that peripheral neuroendocrine mechanisms that regulate memory processing may target their actions toward those neural systems most engaged in the processing of learning and memory. In addition, measurements of acetylcholine release in different memory systems reveals extensive interactions between memory systems, some cooperative and some competitive. These results imply that many neural systems, often characterized as relatively independent, may in fact interact extensively, blurring the dependencies of different memory tasks on specific neural systems.

Acetylcholine↗
PubMed2004

Inactivation of dorsolateral striatum impairs acquisition of response learning in cue-deficient, but not cue-available, conditions.

Rats received bilateral injections of lidocaine or artificial cerebrospinal fluid (aCSF) into the doisolateral striatum 6 min prior to training in either a plus- or T-shaped maze under cue-poor or cue-available conditions. Lidocaine injections significantly impaired acquisition in the cue-poor environments, but not in the cue-available environments. In addition, aCSF control rats trained in a plus-maze in a cue-poor environment reached criterion much more rapidly than did rats trained in a cue-available environment. These findings suggest that cue availability can permit acquisition of response learning in a manner that is not dependent on activity of the striatum. However, in a cue-poor environment, alternate strategies may be less readily available, revealing more efficient striatal involvement in response learning.

Anesthetics, Local↗
PubMed2003

Intra-hippocampal lidocaine injections impair acquisition of a place task and facilitate acquisition of a response task in rats.

While hippocampal lesions impair learning and memory in many tasks, such lesions also enhance learning and memory in other tasks. The present experiment examines the effects of inactivation of the hippocampus with lidocaine prior to learning, to find food in a place or response version of a four-arm plus-shaped maze. Rats received lidocaine injections 6 min prior to training. Rats were trained in a single session to a criterion of 9/10 correct responses. Compared to artificial cerebrospinal fluid (aCSF)-injected controls, rats with intra-hippocampal injections of lidocaine exhibited significantly retarded acquisition of place learning. In marked contrast, rats with intra-hippocampal injections of lidocaine exhibited significantly enhanced acquisition of response learning compared to their controls. In addition to showing that the hippocampus is important for learning the place task, these findings suggest that processing of information by the hippocampus interferes with learning a task dependent on a different neural system.

Anesthetics, Local↗
PubMed2003

Switching memory systems during learning: changes in patterns of brain acetylcholine release in the hippocampus and striatum in rats.

This experiment measured acetylcholine (ACh) release simultaneously in the hippocampus and striatum while rats were trained in a cross maze. Consistent with past findings, rats initially showed learning on the basis of place (i.e., turning to the correct position relative to the room), but after extensive training, rats shifted to learning on the basis of response (i.e., turning to the right/left to find the food). Profiles of ACh release in the hippocampus and striatum were markedly different during training. In the hippocampus, ACh release increased by approximately 60% at the onset of training and remained at that level of release throughout training, even after the rats began to show learning on the basis of turning rather than place. In the striatum, increases in ACh release occurred later, reaching asymptotic increases of 30-40%, coincident with a transition from expressing place learning to expressing response learning. These findings suggest that the hippocampal and striatal systems both participate in learning in this task, but in a manner characterized by differential activation of the neural systems. The hippocampal system is apparently engaged first before the striatum is activated and, to the extent the hippocampus is important for place learning, promotes the use of a place solution to the maze. Later in training, although the hippocampus remains activated, the striatum is also activated in a manner that may enable the use of a response strategy to solve the maze. These findings may offer a neurobiological marker of a transition during skill learning from declarative to procedural learning.

Acetylcholine↗
PubMed2003

Acetylcholine modulation of neural systems involved in learning and memory.

Extensive evidence supports the view that cholinergic mechanisms modulate learning and memory formation. This paper reviews evidence for cholinergic regulation of multiple memory systems, noting that manipulations of cholinergic functions in many neural systems can enhance or impair memory for tasks generally associated with those neural systems. While parallel memory systems can be identified by combining lesions with carefully crafted tasks, most-if not all-tasks require the combinatorial participation of multiple neural systems. This paper offers the hypothesis that the magnitude of acetylcholine (ACh) release in different neural systems may regulate the relative contributions of these systems to learning. Recent studies of ACh release, obtained with in vivo microdialysis samples during training, together with direct injections of cholinergic drugs into different neural systems, provide evidence that release of ACh is important in engaging these systems during learning, and that the extent to which the systems are engaged is associated with individual differences in learning and memory.

Amygdala↗
PubMed2003

Patterns of brain acetylcholine release predict individual differences in preferred learning strategies in rats.

Acetylcholine release was measured simultaneously in the hippocampus and dorsal striatum of rats before and during training on a maze that could be learned using either a hippocampus-dependent spatial strategy or a dorsal striatum-dependent turning strategy. A probe trial administered after rats reached a criterion of 9/10 correct responses revealed that about half of the rats used a spatial strategy and half a turning strategy to solve the task. Acetylcholine release in the hippocampus, as well as the ratio of acetylcholine release in the hippocampus vs. the dorsal striatum, measured either before or during training, predicted these individual differences in strategy selection during learning. These findings suggest that differences in release of acetylcholine across brain areas may provide a neurobiological marker of individual differences in selection of the strategies rats use to solve a learning task.

Acetylcholine↗
PubMed2003

Cooperation between memory systems: acetylcholine release in the amygdala correlates positively with performance on a hippocampus-dependent task.

The present experiment examined the relationship between release of acetylcholine (ACh) in the amygdala and performance on a hippocampus-dependent spatial working memory task. Using in vivo microdialysis, the authors measured ACh release in rats during testing on a spontaneous alternation task. Amygdala ACh release was positively correlated with performance on the hippocampus-dependent task. These findings suggest that activation of the amygdala promotes processing in other neural systems important for learning and memory.

Acetylcholine↗