A GENETIC CONTROL OF THE NUMBER OF CENTRAL DOPAMINE NEURONS IN RELATIONSHIP TO BRAIN ORGANIZATION, DRUG RESPONSES, AND BEHAVIOR

1979 ◽  
pp. 23-33 ◽  
Author(s):  
Donald J. Reis ◽  
Harriet Baker ◽  
J. Stephen Fink ◽  
Tong H. Joh
Keyword(s):  
Genetic Control ◽  
Dopamine Neurons ◽  
Brain Organization ◽  
Drug Responses ◽  
Central Dopamine Neurons ◽  
And Behavior

scholarly journals The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Patricia Bermudez-Martin ◽  
Jérôme A. J. Becker ◽  
Nicolas Caramello ◽  
Sebastian P. Fernandez ◽  
Renan Costa-Campos ◽  
...  
Keyword(s):  
Social Behavior ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
Dopamine Neurons ◽  
Therapeutic Interventions ◽  
Microbiota Composition ◽  
Microbial Metabolite ◽  
Central Dopamine Neurons ◽  
Induced Changes

Abstract Background Autism spectrum disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis, changes in microbiota composition as well as in the fecal, serum, and urine levels of microbial metabolites. Yet a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice. Results Mice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol excretion, compared to mice transplanted with the microbiota of control mice. In addition, we identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability, and fecal p-Cresol levels when transplanted to p-Cresol-treated mice. Conclusions The microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production to treat patients with ASD.

scholarly journals Distinct roles for dopamine clearance mechanisms in regulating behavioral flexibility

2021 ◽  
Author(s):  
Clio Korn ◽  
Thomas Akam ◽  
Kristian H. R. Jensen ◽  
Cristiana Vagnoni ◽  
Anna Huber ◽  
...  
Keyword(s):  
Decision Making ◽  
Behavioral Flexibility ◽  
Dopamine Neurons ◽  
Nucleus Accumbens Core ◽  
Comt Inhibition ◽  
Improved Performance ◽  
Dopamine Signaling ◽  
Precise Relationship ◽  
And Behavior ◽  
Kinetics Of

AbstractDopamine plays a crucial role in adaptive behavior, and dysfunctional dopamine is implicated in multiple psychiatric conditions characterized by inflexible or inconsistent choices. However, the precise relationship between dopamine and flexible decision making remains unclear. One reason is that, while many studies have focused on the activity of dopamine neurons, efficient dopamine signaling also relies on clearance mechanisms, notably the dopamine transporter (DAT), which predominates in striatum, and catechol-O-methyltransferase (COMT), which predominates in cortex. The exact locus, extent, and timescale of the effects of DAT and COMT are uncertain. Moreover, there is limited data on how acute disruption of either mechanism affects flexible decision making strategies mediated by cortico-striatal networks. To address these issues, we combined pharmacological modulation of DAT and COMT with electrochemistry and behavior in mice. DAT blockade, but not COMT inhibition, regulated sub-second dopamine release in the nucleus accumbens core, but surprisingly neither clearance mechanism affected evoked release in prelimbic cortex. This was not due to a lack of sensitivity, as both amphetamine and atomoxetine changed the kinetics of sub-second release. In a multi-step decision making task where mice had to respond to reversals in either reward probabilities or the choice sequence to reach the goal, DAT blockade selectively impaired, and COMT inhibition improved, performance after reward reversals, but neither manipulation affected the adaptation of choices after action-state transition reversals. Together, our data suggest that DAT and COMT shape specific aspects of behavioral flexibility by regulating different aspects of the kinetics of striatal and cortical dopamine, respectively.

Normalization Principles in Computational Neuroscience

2019 ◽  
Author(s):  
Kenway Louie ◽  
Paul W. Glimcher
Keyword(s):  
Information Processing ◽  
Computational Neuroscience ◽  
Linear Models ◽  
Brain Regions ◽  
Information Coding ◽  
Brain Organization ◽  
Contextual Modulation ◽  
Early Visual Cortex ◽  
And Function ◽  
And Behavior

A core question in systems and computational neuroscience is how the brain represents information. Identifying principles of information coding in neural circuits is critical to understanding brain organization and function in sensory, motor, and cognitive neuroscience. This provides a conceptual bridge between the underlying biophysical mechanisms and the ultimate behavioral goals of the organism. Central to this framework is the question of computation: what are the relevant representations of input and output, and what algorithms govern the input-output transformation? Remarkably, evidence suggests that certain canonical computations exist across different circuits, brain regions, and species. Such computations are implemented by different biophysical and network mechanisms, indicating that the unifying target of conservation is the algorithmic form of information processing rather than the specific biological implementation. A prime candidate to serve as a canonical computation is divisive normalization, which scales the activity of a given neuron by the activity of a larger neuronal pool. This nonlinear transformation introduces an intrinsic contextual modulation into information coding, such that the selective response of a neuron to features of the input is scaled by other input characteristics. This contextual modulation allows the normalization model to capture a wide array of neural and behavioral phenomena not captured by simpler linear models of information processing. The generality and flexibility of the normalization model arises from the normalization pool, which allows different inputs to directly drive and suppress a given neuron, effectively separating information that drives excitation and contextual modulation. Originally proposed to describe responses in early visual cortex, normalization has been widely documented in different brain regions, hierarchical levels, and modalities of sensory processing; furthermore, recent work shows that the normalization extends to cognitive processes such as attention, multisensory integration, and decision making. This ubiquity reinforces the canonical nature of the normalization computation and highlights the importance of an algorithmic framework in linking biological mechanism and behavior.

NEUROBIOLOGICAL UNDERPINNINGS OF LANGUAGE IN AUTISM SPECTRUM DISORDERS

2008 ◽  
Vol 28 ◽  
pp. 128-149 ◽  
Author(s):  
Inge-Marie Eigsti ◽  
Jillian M. Schuh
Keyword(s):  
Cognitive Task ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Behavioral Differences ◽  
Brain Organization ◽  
Communicative Skills ◽  
Complex Cognitive Task ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Brain

As a neurodevelopmental disorder, autism is characterized by impairments and differences at the levels of both brain and behavior. Communicative impairments in autism are a core feature of the disorder, and a rapidly expanding literature is exploring language in autism using the tools of cognitive neuroscience, particularly electroencephalography and brain imaging. Recent research indicates consistent differences in the degree to which language-specific processes are lateralized in the brain, and it also suggests that language impairments are linked to differences in brain structure that may lead to inefficient coordination of activity between different neural assemblies to achieve a complex cognitive task, defined as functional connectivity. We review findings from current work and suggest that neurobiological data are critical in our ability to understand the mechanisms underlying behavioral differences in communicative skills. Going beyond simple dichotomies between delayed versus deviant development, we can use such data to ask whether behavior reflects processes that are merely inefficient or, instead, whether impairments at the behavioral level reflect fundamental differences in brain organization and the networks involved in various tasks.

Interaction of benzodiazepines with neuroleptics at central dopamine neurons

1976 ◽  
Vol 294 (1) ◽  
pp. 1-7 ◽  
Author(s):  
H. H. Keller ◽  
R. Schaffner ◽  
W. Haefely
Keyword(s):  
Dopamine Neurons ◽  
Central Dopamine Neurons

scholarly journals Brain Plasticity and Behavior

2003 ◽  
Vol 12 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Bryan Kolb ◽  
Robbin Gibb ◽  
Terry E. Robinson
Keyword(s):  
Brain Plasticity ◽  
Recovery Of Function ◽  
Psychological Disorders ◽  
Abnormal Behavior ◽  
Brain Organization ◽  
Functional Changes ◽  
Brain Circuitry ◽  
And Function ◽  
And Behavior ◽  
The Brain

Although the brain was once seen as a rather static organ, it is now clear that the organization of brain circuitry is constantly changing as a function of experience. These changes are referred to as brain plasticity, and they are associated with functional changes that include phenomena such as memory, addiction, and recovery of function. Recent research has shown that brain plasticity and behavior can be influenced by a myriad of factors, including both pre- and postnatal experience, drugs, hormones, maturation, aging, diet, disease, and stress. Understanding how these factors influence brain organization and function is important not only for understanding both normal and abnormal behavior, but also for designing treatments for behavioral and psychological disorders ranging from addiction to stroke.

scholarly journals Models of heterogeneous dopamine signaling in an insect learning and memory center

2019 ◽  
Author(s):  
Linnie Jiang ◽  
Ashok Litwin-Kumar
Keyword(s):  
Mushroom Body ◽  
Internal State ◽  
Dopamine Neurons ◽  
Insect Learning ◽  
External Reinforcement ◽  
Learned Behaviors ◽  
Architectural Constraints ◽  
Dopamine Signaling ◽  
And Behavior ◽  
Task Parameters

AbstractThe Drosophila mushroom body exhibits dopamine dependent synaptic plasticity that underlies the acquisition of associative memories. Recordings of dopamine neurons in this system have identified signals related to external reinforcement such as reward and punishment. However, other factors including locomotion, novelty, reward expectation, and internal state have also recently been shown to modulate dopamine neurons. This heterogeneity is at odds with typical modeling approaches in which these neurons are assumed to encode a global, scalar error signal. How is dopamine dependent plasticity coordinated in the presence of such heterogeneity? We develop a modeling approach that infers a pattern of dopamine activity sufficient to solve defined behavioral tasks, given architectural constraints informed by knowledge of mushroom body circuitry. Model dopamine neurons exhibit diverse tuning to task parameters while nonetheless producing coherent learned behaviors. Our results provide a mechanistic framework that accounts for the heterogeneity of dopamine activity during learning and behavior.

Central dopamine neurons and sensory processing

1974 ◽  
Vol 11 ◽  
pp. 149-150 ◽  
Author(s):  
Urban Ungerstedt ◽  
Tomas Ljungberg
Keyword(s):  
Sensory Processing ◽  
Dopamine Neurons ◽  
Central Dopamine Neurons

Ontogenetic Shifts in Brain Organization in the Bluespotted Stingray Neotrygon kuhlii (Chondrichthyes: Dasyatidae)

2017 ◽  
Vol 89 (2) ◽  
pp. 68-83 ◽  
Author(s):  
Thomas J. Lisney ◽  
Kara E. Yopak ◽  
Victoria Camilieri-Asch ◽  
Shaun P. Collin
Keyword(s):  
Body Size ◽  
Sexual Maturity ◽  
Initial Growth ◽  
Brain Growth ◽  
Olfactory Bulbs ◽  
Brain Areas ◽  
Brain Organization ◽  
Ontogenetic Shifts ◽  
And Behavior ◽  
The Brain

Fishes exhibit lifelong neurogenesis and continual brain growth. One consequence of this continual growth is that the nervous system has the potential to respond with enhanced plasticity to changes in ecological conditions that occur during ontogeny. The life histories of many teleost fishes are composed of a series of distinct stages that are characterized by shifts in diet, habitat, and behavior. In many cases, these shifts correlate with changes in overall brain growth and brain organization, possibly reflecting the relative importance of different senses and locomotor performance imposed by the new ecological niches they encounter throughout life. Chondrichthyan (cartilaginous) fishes also undergo ontogenetic shifts in habitat, movement patterns, diet, and behavior, but very little is known about any corresponding shifts in the size and organization of their brains. Here, we investigated postparturition ontogenetic changes in brain-body size scaling, the allometric scaling of seven major brain areas (olfactory bulbs, telencephalon, diencephalon, optic tectum, tegmentum, cerebellum, and medulla oblongata) relative to the rest of the brain, and cerebellar foliation in a chondrichthyan, i.e., the bluespotted stingray Neotrygon kuhlii. We also investigated the unusual morphological asymmetry of the cerebellum in this and other batoids. As in teleosts, the brain continues to grow throughout life, with a period of rapid initial growth relative to body size, before slowing considerably at the onset of sexual maturity. The olfactory bulbs and the cerebellum scale with positive allometry relative to the rest of the brain, whereas the other five brain areas scale with varying degrees of negative allometry. None of the major brain areas showed the stage-specific differences in rates of growth often found in teleosts. Cerebellar foliation also increases at a faster rate than overall brain growth. We speculate that changes in the olfactory bulbs and cerebellum could reflect increased olfactory and locomotor capabilities, which may be associated with ontogenetic shifts in diet, habitat use, and activity patterns, as well as shifts in behavior that occur with the onset of sexual maturity. The frequency distributions of the three cerebellar morphologies exhibited in this species best fit a 2:1:1 (right-sided:left-sided:intermediate) distribution, mirroring previous findings for another stingray species.

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