Circuit mechanisms for chemical modulation of cortex-wide network interactions and exploration behavior

AbstractInfluential accounts postulate distinct roles of the catecholamine and acetylcholine neuromodulatory systems in cognition and behavior. But previous work found similar effects of these modulators on the response properties of individual cortical neurons. Here, we report a double dissociation between catecholamine and acetylcholine effects at the level of cortex-wide network interactions in humans. A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not rest. Conversely, an acetylcholine-boost decreased correlations during rest, but not task. Cortical circuit modeling explained this dissociation by differential changes in two circuit properties: the local excitation-inhibition balance (more strongly altered by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine). The inferred catecholaminergic mechanism also predicted increased behavioral exploration, which we confirmed in human behavior during both a perceptual and value-based choice task. In sum, we identified specific circuit mechanisms for shaping cortex-wide network interactions and behavior by key neuromodulatory systems.

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Circuit mechanisms for the chemical modulation of cortex-wide network interactions and behavioral variability

Science Advances ◽

10.1126/sciadv.abf5620 ◽

2021 ◽

Vol 7 (29) ◽

pp. eabf5620

Author(s):

Thomas Pfeffer ◽

Adrian Ponce-Alvarez ◽

Konstantinos Tsetsos ◽

Thomas Meindertsma ◽

Christoffer Julius Gahnström ◽

...

Keyword(s):

Cortical Neurons ◽

Large Scale ◽

Choice Behavior ◽

Circuit Modeling ◽

Behavioral Variability ◽

Double Dissociation ◽

Cortical Areas ◽

Cortical Circuit ◽

Chemical Modulation ◽

And Behavior

Influential theories postulate distinct roles of catecholamines and acetylcholine in cognition and behavior. However, previous physiological work reported similar effects of these neuromodulators on the response properties (specifically, the gain) of individual cortical neurons. Here, we show a double dissociation between the effects of catecholamines and acetylcholine at the level of large-scale interactions between cortical areas in humans. A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not rest. An acetylcholine boost decreased interactions during rest, but not task. Cortical circuit modeling explained this dissociation by differential changes in two circuit properties: the local excitation-inhibition balance (more strongly increased by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine). The inferred catecholaminergic mechanism also predicted noisier decision-making, which we confirmed for both perceptual and value-based choice behavior. Our work highlights specific circuit mechanisms for shaping cortical network interactions and behavioral variability by key neuromodulatory systems.

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Perinatal fentanyl exposure leads to long-lasting impairments in somatosensory circuit function and behavior

10.1101/2020.09.19.304352 ◽

2020 ◽

Author(s):

Jason Alipio ◽

Catherine Haga ◽

Megan E Fox ◽

Keiko Arakawa ◽

Rakshita Balaji ◽

...

Keyword(s):

Cortical Neurons ◽

Morphological Changes ◽

Anterior Cingulate ◽

Preclinical Model ◽

Sensory Stimuli ◽

Synaptic Excitation ◽

Molecular Abnormalities ◽

Postsynaptic Currents ◽

And Behavior

One consequence of the opioid epidemic are lasting neurodevelopmental sequelae afflicting adolescents exposed to opioids in the womb. A translationally relevant and developmentally accurate preclinical model is needed to understand the behavioral, circuit, network, and molecular abnormalities resulting from this exposure. By employing a novel preclinical model of perinatal fentanyl exposure, our data reveal that fentanyl has several dose-dependent, developmental consequences to somatosensory function and behavior. Newborn male and female mice exhibit signs of withdrawal and sensory-related deficits that extend at least to adolescence. As fentanyl exposure does not affect dams' health or maternal behavior, these effects result from the direct actions of perinatal fentanyl on the pups' developing brain. At adolescence, exposed mice exhibit reduced adaptation to sensory stimuli, and a corresponding impairment in primary somatosensory (S1) function. In vitro electrophysiology demonstrates a long-lasting reduction in S1 synaptic excitation, evidenced by decreases in release probability, NMDA receptor-mediated postsynaptic currents, and frequency of miniature excitatory postsynaptic currents, as well as increased frequency of miniature inhibitory postsynaptic currents. In contrast, anterior cingulate cortical neurons exhibit an opposite phenotype, with increased synaptic excitation. Consistent with these changes, electrocorticograms reveal suppressed ketamine-evoked γ oscillations. Morphological analysis of S1 pyramidal neurons indicate reduced dendritic complexity, dendritic length, and soma size. Further, exposed mice exhibited abnormal cortical mRNA expression of key receptors and neuronal growth and development, changes that were consistent with the electrophysiological and morphological changes. These findings demonstrate the lasting sequelae of perinatal fentanyl exposure on sensory processing and function.

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Inferring cortical function in the mouse visual system through large-scale systems neuroscience

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1512901113 ◽

2016 ◽

Vol 113 (27) ◽

pp. 7337-7344 ◽

Cited By ~ 48

Author(s):

Michael Hawrylycz ◽

Costas Anastassiou ◽

Anton Arkhipov ◽

Jim Berg ◽

Michael Buice ◽

...

Keyword(s):

Cortical Neurons ◽

Large Scale ◽

Model Organism ◽

Building Blocks ◽

Mammalian Brain ◽

Cortical Function ◽

Scientific Mission ◽

Large Populations ◽

Cell Type Specific ◽

And Behavior

The scientific mission of the Project MindScope is to understand neocortex, the part of the mammalian brain that gives rise to perception, memory, intelligence, and consciousness. We seek to quantitatively evaluate the hypothesis that neocortex is a relatively homogeneous tissue, with smaller functional modules that perform a common computational function replicated across regions. We here focus on the mouse as a mammalian model organism with genetics, physiology, and behavior that can be readily studied and manipulated in the laboratory. We seek to describe the operation of cortical circuitry at the computational level by comprehensively cataloging and characterizing its cellular building blocks along with their dynamics and their cell type-specific connectivities. The project is also building large-scale experimental platforms (i.e., brain observatories) to record the activity of large populations of cortical neurons in behaving mice subject to visual stimuli. A primary goal is to understand the series of operations from visual input in the retina to behavior by observing and modeling the physical transformations of signals in the corticothalamic system. We here focus on the contribution that computer modeling and theory make to this long-term effort.

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Prenatal Deletion of the RNA-Binding Protein HuD Disrupts Postnatal Cortical Circuit Maturation and Behavior

Journal of Neuroscience ◽

10.1523/jneurosci.3703-13.2014 ◽

2014 ◽

Vol 34 (10) ◽

pp. 3674-3686 ◽

Cited By ~ 28

Author(s):

E. M. DeBoer ◽

R. Azevedo ◽

T. A. Vega ◽

J. Brodkin ◽

W. Akamatsu ◽

...

Keyword(s):

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Cortical Circuit ◽

And Behavior

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Domestic dogs' gaze and behavior in 2-alternative choice tasks

10.31234/osf.io/pt3vh ◽

2021 ◽

Author(s):

Julia Espinosa ◽

Daphna Buchsbaum

Keyword(s):

Decision Making ◽

Visual Discrimination ◽

Visual Information ◽

Choice Behavior ◽

Choice Task ◽

Domestic Dogs ◽

The World ◽

Alternative Choice ◽

And Behavior ◽

Choice Tasks

Species such as humans rely on their excellent visual abilities to perceive and navigate the world. Dogs have co-habited with humans for millennia, yet we know little about how they gather and use visual information to guide decision-making. Across five experiments, we presented pet dogs (N=49) with two foods of unequal value in a 2-alternative choice task, and measured whether dogs showed preferential gazing, and whether visual attention patterns were associated with item choice. Overall, dogs looked significantly longer at the preferred (high value) food over the low value alternative. There was also evidence of item-dependent predictive gaze—dogs looked proportionally longer at the item they subsequently chose. Surprisingly, dogs’ choice behavior was only slightly above chance, despite visual discrimination. These results suggest that dogs use visual information in the environment to inform their choice behavior, but that other factors may also contribute to their decision-making.

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GABA—from Inhibition to Cognition: Emerging Concepts

The Neuroscientist ◽

10.1177/1073858417734530 ◽

2017 ◽

Vol 24 (5) ◽

pp. 501-515 ◽

Cited By ~ 18

Author(s):

T. Schmidt-Wilcke ◽

E. Fuchs ◽

K. Funke ◽

A. Vlachos ◽

F. Müller-Dahlhaus ◽

...

Keyword(s):

Cortical Neurons ◽

Brain Regions ◽

Mammalian Brain ◽

Resonance Spectroscopy ◽

Inhibitory Neurotransmitter ◽

Electrophysiological Properties ◽

Potential Strategy ◽

The One ◽

And Behavior

Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA.

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Developmental Cortical Plasticity in the Central Auditory System

The Oxford Handbook of Developmental Neural Plasticity ◽

10.1093/oxfordhb/9780190635374.013.1 ◽

2018 ◽

Author(s):

Michele N. Insanally ◽

Robert C. Froemke

Keyword(s):

Cortical Plasticity ◽

Life Experience ◽

Acoustic Environment ◽

Early Life Experience ◽

Inhibitory Circuitry ◽

System P ◽

Cortical Circuit ◽

And Behavior ◽

The Brain

The brain has a tremendous ability to change as a result of experience. While the brain is plastic throughout life, during early development, the nervous system seems much more sensitive to changes in neural activity or experience. During postnatal critical or sensitive periods, sensory experience can significantly restructure cortical networks, leading to long-term changes in central representations that can affect perception and behavior. This chapter reviews how the parameters of the acoustic environment and inhibitory circuitry can regulate cortical plasticity during early life experience. It highlights newly identified cortical circuit elements that are specifically recruited to engage critical-period plasticity mechanisms.

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