Associative Learning and Prefrontal Synaptic Plasticity Dysfunction in Schizophrenia

The altered glutamatergic and DA transmission proposed for schizophrenia may affect synaptic plasticity mechanisms in the PFC. A reduction of dendritic spines in PFC pyramidal neurons has been reported in schizophrenia brains (Glantz and Lewis, 2000) as well as in animals with a neonatal VH lesion (Lipska et al., 2001a), suggesting reduced excitatory synaptic inputs in this area. Decreases of N-acetyl aspartate (NAA) in schizophrenia (Bertolino et al., 1999) and in this animal model (Bertolino...

Dopamine Controls LTP Induction and Expression

Memory And Ltp Nature

Infusion of dopamine (1 mM) in the PFC through reverse microdialysis (see Section 4.2) prior to the application of tetanus in the hippocampus increases the magnitude (two folds) of LTP in the PFC, and this greater LTP is maintained over time. Comparable results can also be obtained with the application of nomifensine (5nM), a dopamine reuptake blocker known to increase and prolong dopamine release, and these effects are pronounced at very low concentration (Jay et al., 1996a, b). 4.1.1...

Concluding Remarks

The number of TMS studies addressing episodic long-term memory in humans is still limited. However, all of them converge to indicating that the PFC plays an important role in long-term episodic memory. These results, therefore, extend the concept that the prefrontal regions are mainly devoted to short-term and working memory processes. An important qualification is that the functional role of PFC appears to be limited to the memory processing of novel information. In addition, they consistently...

References

Alvarez P, Eichenbaum H (2002) Representations of odors in the rat orbitofrontal cortex change during and after learning. Behav Neurosci 116 421-433. Arnsten AF (1997) Catecholamine regulation of the prefrontal cortex. J Psychopharmacol 11 151-162. Baxter MG, Parker A, Lindner CCC, Izquierdo AD, Murray EA (2000). Control of response selection by reinforcer value requires interaction of amygdala and orbitofrontal cortex. J Neurosci 20 4311-4319. Beaulieu C, Colonnier M (1987) Effect of the...

Cerebral Plasticity after Prefrontal Lesions

There is an extensive literature examining the effect of prefrontal injury during development on the structure and function of the remaining brain (e.g. Kolb, 1995). The details of these studies are beyond the scope of this chapter, so we will review this topic only briefly and with emphasis upon synaptic plasticity (for more thorough review, see Kolb and Gibb, 2001). As a general rule, damage to the medial or orbital subfields of the rat PFC between about 7-12 days of age produce markedly...

Frontal Lobe Plasticity in the Injured Brain

When the brain is injured, there are likely to be compensatory changes in the remaining neural networks that will reflect either the reorganization of existing circuits or the creation of new circuits, most likely reflecting the formation of new connections among remaining neurons. Because the PFC is connected with most of the posterior cortical regions, as well as the motor regions of the frontal lobe, it seems reasonable to predict that damage to other cerebral regions will influence the...

Effects of Gonadal Hormones

One consistent finding in studies of the effects of prefrontal lesions in rats is that there are sex-related differences in the effects of injury to both the mPFC and OFC (e.g. Kolb and Cioe, 1996), a result that is similar to observations in both humans (e.g. Kimura, 1999) and rhesus monkeys (Clark and Goldman-Rakic, 1989). This leads to the possibility that there might be sex-related differences in the structure of cells in the mPFC and or OFC. There are. Males show more extensive dendritic...

Effects of Sensory and Motor Experience

There is an extensive literature showing that the structure of cortical neurons is influenced by various types of sensory and motor experience (for a review, see Kolb and Whishaw, 1998). For example, if laboratory animals ranging from rats to cats and monkeys are placed in complex environments versus living in standard lab cages, there are large changes in dendritic length and synapse number throughout the primary visual and somatosensory cortex (e.g. Greenough et al., 1985 Beaulieu and...

Plasticity And The Prefrontal Cortex Of The

In thinking about the relationship between brain and behavior, there is a tendency to focus on constancy, rather than on change, and on similarities, rather than on differences. Thus, as we try to find parallels between the organizations of the frontal regions in different species of mammals, we focus on the constancies and similarities in the organization and function across species. But another way to examine brain-behavior relations is to focus on variability and change in organization. The...

Effects of Lesions to the OFC

There is much more parsimony in reviews comparing the effects of OFC lesions in rodents and primates (e.g. Schoenbaum and Setlow, 2002). The OFC receives significant olfactory and taste input, and although OFC lesions do not produce deficits in olfactory or taste discriminations, they do produce deficits in tasks requiring working memory for odor or taste information (e.g. Otto and Eichenbaum, 1992 DeCoteau et al., 1997 Ragozzino and Kesner, 1999). Furthermore, lesions to the OFC disrupt the...

Effects of Lesions to the mPFC

It was demonstrated in the early 1970s that lesions to the mPFC and OFC in rats produced very different behavioral syndromes, and that these behavioral changes were strikingly similar to those observed in primates with lesions to the dorsolateral and OFC regions, respectively (Table 1 for reviews see Kolb, 1984, 1990). For example, damage to the mPFC area produces severe deficits in acquisition and retention of working memory tasks such as delayed response (Kolb et al., 1974), delayed...

Cholinergic and Monoaminergic Gating Systems

The PFC of rats and primates plays a role in gating the inputs of the cholinergic and monoaminergic systems to the rest of the cerebral mantle (e.g. Ragozzino, 2000). Thus, although the entire neocortex receives inputs from cholinergic, noradrenergic, and serotinergic systems, only the PFC sends reciprocal connections to the basal forebrain, locus coeruleus, and the dorsal and median raphe (e.g. Uylings and Van Eden, 1990 Arnsten, 1997 Everitt and Robbins, 1997). This feedback system is...

Whither The Prefrontal Cortex Of The

It is less obvious just what the class-common functions of the frontal cortex might be, but we would anticipate that if the frontal cortex of mammals developed because all mammals face common functional problems, then we should be able to identify class-common functions of the frontal cortex. One place to begin searching for class-common frontal functions is to consider what animals use sensory inputs for. The most obvious function is to guide behavior on line, such as in the visuomotor control...

Introduction

One of the major obstacles in comparing the behavior of different species of mammals is that each species has a unique behavioral repertoire that permits the animal to survive in its particular environmental niche. There is, therefore, the danger that neocortical organization is uniquely patterned in different species in a way that reflects the unique behavioral adaptation of those different species. One way to address this problem is to recognize that although the details of behavior may...

Effects of Drugs and Natural Reinforcers

Many people commonly take stimulant drugs like nicotine, amphetamine, cocaine, or depressant drugs like morphine or alcohol, all of which affect behavior and are thus said to be psychoactive. The long-term consequences of abusing psychoactive drugs are now well-documented, and it has been hypothesized that some of the behavioral symptoms observed in drug addicts or alcoholics are related to abnormalities in the functioning of the prefrontal regions (Robbins and Everitt, 2002). One experimental...

Tms Studies On Episodic Longterm Memory

Despite the increasing interest in TMS as one of the most attractive tools for neuroscientists (Chicurel, 2002), its application to the investigation of episodic long-term memory is still limited. A Medline search in the first week of the year 2003, using TMS rTMS, prefrontal cortex, and memory as keywords, detected the articles most of which deal with verbal visual working memory (n 5) and saccadic eye movements (n 3). Among remaining papers, only four articles (one of which is a review) fully...

Kuei Yuan TSENG

Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY, USA This volume, Prefrontal Cortex from Synaptic Plasticity to Cognition, is an interdisciplinary approach to characterize the function of the anterior portion of the frontal lobe in rodents and human and non-human primates. The specific topics discussed in the chapters of this volume are purposefully diverse they range from membrane properties of prefrontal neurons to cognitive psychology. Nevertheless, this...

Working Memory Task

And Genome Sequencing

To examine neuronal mechanisms of working memory processes, singleneuron activities recorded from DLPFC have been analyzed while monkeys performed a variety of working memory tasks. The working memory task often selected for neurophysiological experiments is the delayed-response task, because the delayed-response task requires working memory of spatial position (Goldman-Rakic, 1987 Funahashi and Kubota, 1994 Fuster, 1997) and because delayed-response deficits have been observed by the selective...

Potential Involvement in Schizophrenia

Yukiori Goto, Kuei-Yuan Tseng, Barbara L. Lewis, and Patricio Center for Neuropharmacology and Neuroscience, Albany Medical Keywords Prefrontal cortex, dopamine, glutamate, membrane potential, ensemble coding, schizophrenia, animal model, synaptic plasticity, in vivo intracellular recording, in vitro whole cell recording. Abstract The prefrontal cortex has been implicated in executive functions, and it can become dysfunctional in psychiatric disorders such as schizophrenia. Prefrontal pyramidal...

The Overdose Hypothesis In Parkinsons Disease Its Relevance To Cognition And The Inverted Ushaped Dopamine Function

An alternative approach to assessing the role of DA in human cognition is to study those clinical disorders in which the DA system is highly compromised. Parkinson's disease (PD) is a progressive neurodegenerative disorder, mainly characterized by motor symptoms. The primary pathology is cell loss in the substantia nigra leading to severe DA loss in the dorsal parts of the striatum as well as additional DA loss in the PFC. Although the disease is mainly a movement disorder, patients also...

Relationship between Depressive State and Reduced Dopaminergic and Serotonergic Transmission

To clarify the involvement of the reduction in serotonergic and dopaminergic transmission in the PFC in the chronic stress-induced depressive state, the beneficial effects of the serotonergic antidepressant, trazodone and those of SKF 81297 were examined. As shown in Figure 7, the chronic stress-induced impairment of rotarod performance was ameliorated by trazodone in a dose-dependent manner. Since the traction performance and locomotor activity were not affected by trazodone, the ameliorative...

Acquisition of New Behaviors and Memory Formation

Having illustrated that i) behavioral and perceptual representations interact bi-directionally, suggesting integrative processing, and that ii) PFC is a necessary structure to temporally and spatially organize behavior with respect to a perceived context, I will now address the question of large-scale brain oscillations during integrative processing. It was suggested earlier in this chapter that macroscopic PFC networks act to link highly processed sensory information to action representations...

The Contribution Of The Pfc To Working Memory Not Shortterm Memory

In 1936, Jacobsen first demonstrated that lesions of the PFC of primates impair performance of the delayed-response working memory task and this finding has been replicated by numerous investigators (see Funahashi and Kubota, 1994 for review). However, there has been considerable difficulty in understanding the nature of this deficit. Working memory and short-term memory have been related theoretically, and therefore there has been a lasting tendency to view working memory processes mediated by...