3,838 research outputs found
Dopaminergic Regulation of Neuronal Circuits in Prefrontal Cortex
Neuromodulators, like dopamine, have considerable influence on the\ud
processing capabilities of neural networks. \ud
This has for instance been shown in the working memory functions\ud
of prefrontal cortex, which may be regulated by altering the\ud
dopamine level. Experimental work provides evidence on the biochemical\ud
and electrophysiological actions of dopamine receptors, but there are few \ud
theories concerning their significance for computational properties \ud
(ServanPrintzCohen90,Hasselmo94).\ud
We point to experimental data on neuromodulatory regulation of \ud
temporal properties of excitatory neurons and depolarization of inhibitory \ud
neurons, and suggest computational models employing these effects.\ud
Changes in membrane potential may be modelled by the firing threshold,\ud
and temporal properties by a parameterization of neuronal responsiveness \ud
according to the preceding spike interval.\ud
We apply these concepts to two examples using spiking neural networks.\ud
In the first case, there is a change in the input synchronization of\ud
neuronal groups, which leads to\ud
changes in the formation of synchronized neuronal ensembles.\ud
In the second case, the threshold\ud
of interneurons influences lateral inhibition, and the switch from a \ud
winner-take-all network to a parallel feedforward mode of processing.\ud
Both concepts are interesting for the modeling of cognitive functions and may\ud
have explanatory power for behavioral changes associated with dopamine \ud
regulation
Presynaptic modulation as fast synaptic switching: state-dependent modulation of task performance
Neuromodulatory receptors in presynaptic position have the ability to
suppress synaptic transmission for seconds to minutes when fully engaged. This
effectively alters the synaptic strength of a connection. Much work on
neuromodulation has rested on the assumption that these effects are uniform at
every neuron. However, there is considerable evidence to suggest that
presynaptic regulation may be in effect synapse-specific. This would define a
second "weight modulation" matrix, which reflects presynaptic receptor efficacy
at a given site. Here we explore functional consequences of this hypothesis. By
analyzing and comparing the weight matrices of networks trained on different
aspects of a task, we identify the potential for a low complexity "modulation
matrix", which allows to switch between differently trained subtasks while
retaining general performance characteristics for the task. This means that a
given network can adapt itself to different task demands by regulating its
release of neuromodulators. Specifically, we suggest that (a) a network can
provide optimized responses for related classification tasks without the need
to train entirely separate networks and (b) a network can blend a "memory mode"
which aims at reproducing memorized patterns and a "novelty mode" which aims to
facilitate classification of new patterns. We relate this work to the known
effects of neuromodulators on brain-state dependent processing.Comment: 6 pages, 13 figure
Could dopamine agonists aid in drug development for anorexia nervosa?
Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways
Catecholamines and cognition after traumatic brain injury
Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a personâs catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ânetworksâ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner
Dopamine modulation of learning and memory in the prefrontal cortex: insights from studies in primates, rodents, and birds
In this review, we provide a brief overview over the current knowledge about the role of dopamine transmission in the prefrontal cortex during learning and memory. We discuss work in humans, monkeys, rats, and birds in order to provide a basis for comparison across species that might help identify crucial features and constraints of the dopaminergic system in executive function. Computational models of dopamine function are introduced to provide a framework for such a comparison. We also provide a brief evolutionary perspective showing that the dopaminergic system is highly preserved across mammals. Even birds, following a largely independent evolution of higher cognitive abilities, have evolved a comparable dopaminergic system. Finally, we discuss the unique advantages and challenges of using different animal models for advancing our understanding of dopamine function in the healthy and diseased brain
Reward learning as a potential target for pharmacological augmentation of cognitive remediation for schizophrenia: a roadmap for preclinical development.
RationaleImpaired cognitive abilities are a key characteristic of schizophrenia. Although currently approved pharmacological treatments have demonstrated efficacy for positive symptoms, to date no pharmacological treatments successfully reverse cognitive dysfunction in these patients. Cognitively-based interventions such as cognitive remediation (CR) and other psychosocial interventions however, may improve some of the cognitive and functional deficits of schizophrenia. Given that these treatments are time-consuming and labor-intensive, maximizing their effectiveness is a priority. Augmenting psychosocial interventions with pharmacological treatments may be a viable strategy for reducing the impact of cognitive deficits in patients with schizophrenia.ObjectiveWe propose a strategy to develop pharmacological treatments that can enhance the reward-related learning processes underlying successful skill-learning in psychosocial interventions. Specifically, we review clinical and preclinical evidence and paradigms that can be utilized to develop these pharmacological augmentation strategies. Prototypes for this approach include dopamine D1 receptor and α7 nicotinic acetylcholine receptor agonists as attractive targets to specifically enhance reward-related learning during CR.ConclusionThe approach outlined here could be used broadly to develop pharmacological augmentation strategies across a number of cognitive domains underlying successful psychosocial treatment
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