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2.
J Neurosci ; 42(45): 8439-8449, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351821

RESUMO

Psychedelic drugs have reemerged as tools to treat several brain disorders. Cultural attitudes toward them are changing, and scientists are once again investigating the neural mechanisms through which these drugs impact brain function. The significance of this research direction is reflected by recent work, including work presented by these authors at the 2022 meeting of the Society for Neuroscience. As of 2022, there were hundreds of clinical trials recruiting participants for testing the therapeutic effects of psychedelics. Emerging evidence suggests that psychedelic drugs may exert some of their long-lasting therapeutic effects by inducing structural and functional neural plasticity. Herein, basic and clinical research attempting to elucidate the mechanisms of these compounds is showcased. Topics covered include psychedelic receptor binding sites, effects of psychedelics on gene expression, and on dendrites, and psychedelic effects on microcircuitry and brain-wide circuits. We describe unmet clinical needs and the current state of translation to the clinic for psychedelics, as well as other unanswered basic neuroscience questions addressable with future studies.


Assuntos
Alucinógenos , Neurociências , Humanos , Alucinógenos/farmacologia , Alucinógenos/uso terapêutico , Encéfalo , Plasticidade Neuronal
3.
Cogn Affect Behav Neurosci ; 23(3): 894-904, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37165181

RESUMO

Traumatic events can lead to lifelong, inflexible adaptations in threat perception and behavior, which characterize posttraumatic stress disorder (PTSD). This process involves associations between sensory cues and internal states of threat and then generalization of the threat responses to previously neutral cues. However, most formulations neglect adaptations to threat that are not specific to those associations. To incorporate nonassociative responses to threat, we propose a computational theory of PTSD based on adaptation to the frequency of traumatic events by using a reinforcement learning momentum model. Recent threat prediction errors generate momentum that influences subsequent threat perception in novel contexts. This model fits primary data acquired from a mouse model of PTSD, in which unpredictable footshocks in one context accelerate threat learning in a novel context. The theory is consistent with epidemiological data that show that PTSD incidence increases with the number of traumatic events, as well as the disproportionate impact of early life trauma. Because the theory proposes that PTSD relates to the average of recent threat prediction errors rather than the strength of a specific association, it makes novel predictions for the treatment of PTSD.

4.
Mol Psychiatry ; 26(6): 1945-1966, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32161363

RESUMO

The SHANK3 gene encodes a postsynaptic scaffold protein in excitatory synapses, and its disruption is implicated in neurodevelopmental disorders such as Phelan-McDermid syndrome, autism spectrum disorder, and schizophrenia. Most studies of SHANK3 in the neocortex and hippocampus have focused on disturbances in pyramidal neurons. However, GABAergic interneurons likewise receive excitatory inputs and presumably would also be a target of constitutive SHANK3 perturbations. In this study, we characterize the prefrontal cortical microcircuit in awake mice using subcellular-resolution two-photon microscopy. We focused on a nonsense R1117X mutation, which leads to truncated SHANK3 and has been linked previously to cortical dysfunction. We find that R1117X mutants have abnormally elevated calcium transients in apical dendritic spines. The synaptic calcium dysregulation is due to a loss of dendritic inhibition via decreased NMDAR currents and reduced firing of dendrite-targeting somatostatin-expressing (SST) GABAergic interneurons. Notably, upregulation of the NMDAR subunit GluN2B in SST interneurons corrects the excessive synaptic calcium signals and ameliorates learning deficits in R1117X mutants. These findings reveal dendrite-targeting interneurons, and more broadly the inhibitory control of dendritic spines, as a key microcircuit mechanism compromised by the SHANK3 dysfunction.


Assuntos
Transtorno do Espectro Autista , Espinhas Dendríticas , Animais , Cálcio , Códon sem Sentido , Camundongos , Proteínas dos Microfilamentos , Proteínas do Tecido Nervoso/genética , Sinapses
5.
Nano Lett ; 20(6): 4073-4083, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32396366

RESUMO

How neuromodulatory transmitters diffuse into the extracellular space remains an unsolved fundamental biological question, despite wide acceptance of the volume transmission model. Here, we report development of a method combining genetically encoded fluorescent sensors with high-resolution imaging and analysis algorithms which permits the first direct visualization of neuromodulatory transmitter diffusion at various neuronal and non-neuronal cells. Our analysis reveals that acetylcholine and monoamines diffuse at individual release sites with a spread length constant of ∼0.75 µm. These transmitters employ varied numbers of release sites, and when spatially close-packed release sites coactivate they can spillover into larger subcellular areas. Our data indicate spatially restricted (i.e., nonvolume) neuromodulatory transmission to be a prominent intercellular communication mode, reshaping current thinking of control and precision of neuromodulation crucial for understanding behaviors and diseases.

6.
Cereb Cortex ; 29(10): 4090-4106, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-30615132

RESUMO

Instrumental behavior is characterized by the selection of actions based on the degree to which they lead to a desired outcome. However, we lack a detailed understanding of how rewarded actions are reinforced and preferentially implemented. In rodents, the medial frontal cortex is hypothesized to play an important role in this process, based in part on its capacity to encode chosen actions and their outcomes. We therefore asked how neural representations of choice and outcome might interact to facilitate instrumental behavior. To investigate this question, we imaged neural ensemble activity in layer 2/3 of the secondary motor region (M2) while mice engaged in a two-choice auditory discrimination task with probabilistic outcomes. Correct choices could result in one of three reward amounts (single, double or omitted reward), which allowed us to measure neural and behavioral effects of reward magnitude, as well as its categorical presence or absence. Single-unit and population decoding analyses revealed a consistent influence of outcome on choice signals in M2. Specifically, rewarded choices were more robustly encoded relative to unrewarded choices, with little dependence on the exact magnitude of reinforcement. Our results provide insight into the integration of past choices and outcomes in the rodent brain during instrumental behavior.


Assuntos
Comportamento de Escolha/fisiologia , Córtex Motor/fisiologia , Neurônios/fisiologia , Recompensa , Estimulação Acústica , Animais , Discriminação Psicológica/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Imagem Óptica
7.
Nature ; 488(7411): 379-83, 2012 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-22878719

RESUMO

Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (γ-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons.


Assuntos
Interneurônios/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/deficiência , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Channelrhodopsins , Aprendizagem por Discriminação , Camundongos , Modelos Neurológicos , Inibição Neural/fisiologia , Parvalbuminas/metabolismo , Rodopsinas Microbianas/metabolismo , Vigília/fisiologia , Ácido gama-Aminobutírico/metabolismo
9.
bioRxiv ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38328186

RESUMO

Norepinephrine (NE) and acetylcholine (ACh) are neuromodulators that are crucial for learning and decision-making. In the cortex, NE and ACh are released at specific sites along neuromodulatory axons, which would constrain their spatiotemporal dynamics at the subcellular scale. However, how the fluctuating patterns of NE and ACh signaling may be linked to behavioral events is unknown. Here, leveraging genetically encoded NE and ACh indicators, we use two-photon microscopy to visualize neuromodulatory signals in the superficial layer of the mouse medial frontal cortex during decision-making. Head-fixed mice engage in a competitive game called matching pennies against a computer opponent. We show that both NE and ACh transients carry information about decision-related variables including choice, outcome, and reinforcer. However, the two neuromodulators differ in their spatiotemporal pattern of task-related activation. Spatially, NE signals are more segregated with choice and outcome encoded at distinct locations, whereas ACh signals can multiplex and reflect different behavioral correlates at the same site. Temporally, task-driven NE transients were more synchronized and peaked earlier than ACh transients. To test functional relevance, using optogenetics we found that evoked elevation of NE, but not ACh, in the medial frontal cortex increases the propensity of the animals to switch and explore alternate options. Taken together, the results reveal distinct spatiotemporal patterns of rapid ACh and NE transients at the subcellular scale during decision-making in mice, which may endow these neuromodulators with different ways to impact neural plasticity to mediate learning and adaptive behavior.

10.
eNeuro ; 11(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38702188

RESUMO

Norepinephrine (NE), a neuromodulator released by locus ceruleus (LC) neurons throughout the cortex, influences arousal and learning through extrasynaptic vesicle exocytosis. While NE within cortical regions has been viewed as a homogenous field, recent studies have demonstrated heterogeneous axonal dynamics and advances in GPCR-based fluorescent sensors permit direct observation of the local dynamics of NE at cellular scale. To investigate how the spatiotemporal dynamics of NE release in the prefrontal cortex (PFC) affect neuronal firing, we employed in vivo two-photon imaging of layer 2/3 of the PFC in order to observe fine-scale neuronal calcium and NE dynamics concurrently. In this proof of principle study, we found that local and global NE fields can decouple from one another, providing a substrate for local NE spatiotemporal activity patterns. Optic flow analysis revealed putative release and reuptake events which can occur at the same location, albeit at different times, indicating the potential to create a heterogeneous NE field. Utilizing generalized linear models, we demonstrated that cellular Ca2+ fluctuations are influenced by both the local and global NE field. However, during periods of local/global NE field decoupling, the local field drives cell firing dynamics rather than the global field. These findings underscore the significance of localized, phasic NE fluctuations for structuring cell firing, which may provide local neuromodulatory control of cortical activity.


Assuntos
Cálcio , Neurônios , Norepinefrina , Córtex Pré-Frontal , Animais , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/metabolismo , Norepinefrina/metabolismo , Neurônios/fisiologia , Neurônios/metabolismo , Cálcio/metabolismo , Masculino , Potenciais de Ação/fisiologia , Camundongos Endogâmicos C57BL , Camundongos , Feminino
11.
bioRxiv ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38826215

RESUMO

Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in native brain tissues. We therefore developed a pipeline for drug classification using light sheet fluorescence microscopy of immediate early gene expression at cellular resolution followed by machine learning. We tested male and female mice with a panel of drugs, including psilocybin, ketamine, 5-MeO-DMT, 6-fluoro-DET, MDMA, acute fluoxetine, chronic fluoxetine, and vehicle. In one-versus-rest classification, the exact drug was identified with 67% accuracy, significantly above the chance level of 12.5%. In one-versus-one classifications, psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with >95% accuracy. We used Shapley additive explanation to pinpoint the brain regions driving the machine learning predictions. Our results support a novel approach for screening psychoactive drugs with psychedelic properties.

12.
Neurosci Biobehav Rev ; 149: 105158, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37019249

RESUMO

In a social environment, it is essential for animals to consider the behavior of others when making decisions. To quantitatively assess such social decisions, games offer unique advantages. Games may have competitive and cooperative components, modeling situations with antagonistic and shared objectives between players. Games can be analyzed by mathematical frameworks, including game theory and reinforcement learning, such that an animal's choice behavior can be compared against the optimal strategy. However, so far games have been underappreciated in neuroscience research, particularly for rodent studies. In this review, we survey the varieties of competitive and cooperative games that have been tested, contrasting strategies employed by non-human primates and birds with rodents. We provide examples of how games can be used to uncover neural mechanisms and explore species-specific behavioral differences. We assess critically the limitations of current paradigms and propose improvements. Together, the synthesis of current literature highlights the advantages of using games to probe the neural basis of social decisions for neuroscience studies.


Assuntos
Tomada de Decisões , Aprendizagem , Animais , Reforço Psicológico , Comportamento de Escolha
13.
ACS Chem Neurosci ; 14(3): 468-480, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36630309

RESUMO

Psilocybin is a psychedelic with therapeutic potential. While there is growing evidence that psilocybin exerts its beneficial effects through enhancing neural plasticity, the exact brain regions involved are not completely understood. Determining the impact of psilocybin on plasticity-related gene expression throughout the brain can broaden our understanding of the neural circuits involved in psychedelic-evoked neural plasticity. In this study, whole-brain serial two-photon microscopy and light sheet microscopy were employed to map the expression of the immediate early gene, c-Fos, in male and female mice. The drug-induced c-Fos expression following psilocybin administration was compared to that of subanesthetic ketamine and saline control. Psilocybin and ketamine produced acutely comparable elevations in c-Fos expression in numerous brain regions, including anterior cingulate cortex, locus coeruleus, primary visual cortex, central and basolateral amygdala, medial and lateral habenula, and claustrum. Select regions exhibited drug-preferential differences, such as dorsal raphe and insular cortex for psilocybin and the CA1 subfield of hippocampus for ketamine. To gain insights into the contributions of receptors and cell types, the c-Fos expression maps were related to brain-wide in situ hybridization data. The transcript analyses showed that the endogenous levels of Grin2a and Grin2b predict whether a cortical region is sensitive to drug-evoked neural plasticity for both ketamine and psilocybin. Collectively, the systematic mapping approach produced an unbiased list of brain regions impacted by psilocybin and ketamine. The data are a resource that highlights previously underappreciated regions for future investigations. Furthermore, the robust relationships between drug-evoked c-Fos expression and endogenous transcript distributions suggest glutamatergic receptors as a potential convergent target for how psilocybin and ketamine produce their rapid-acting and long-lasting therapeutic effects.


Assuntos
Alucinógenos , Ketamina , Masculino , Feminino , Camundongos , Animais , Ketamina/farmacologia , Psilocibina/farmacologia , Alucinógenos/farmacologia , Alucinógenos/metabolismo , Genes Precoces , Encéfalo/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Núcleo Dorsal da Rafe/metabolismo
14.
eNeuro ; 10(12)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38151324

RESUMO

Dysfunction in the gene SCN2A, which encodes the voltage-gated sodium channel Nav1.2, is strongly associated with neurodevelopmental disorders including autism spectrum disorder and intellectual disability (ASD/ID). This dysfunction typically manifests in these disorders as a haploinsufficiency, where loss of one copy of a gene cannot be compensated for by the other allele. Scn2a haploinsufficiency affects a range of cells and circuits across the brain, including associative neocortical circuits that are important for cognitive flexibility and decision-making behaviors. Here, we tested whether Scn2a haploinsufficiency has any effect on a dynamic foraging task that engages such circuits. Scn2a +/- mice and wild-type (WT) littermates were trained on a choice behavior where the probability of reward between two options varied dynamically across trials and where the location of the high reward underwent uncued reversals. Despite impairments in Scn2a-related neuronal excitability, we found that both male and female Scn2a +/- mice performed these tasks as well as wild-type littermates, with no behavioral difference across genotypes in learning or performance parameters. Varying the number of trials between reversals or probabilities of receiving reward did not result in an observable behavioral difference, either. These data suggest that, despite heterozygous loss of Scn2a, mice can perform relatively complex foraging tasks that make use of higher-order neuronal circuits.


Assuntos
Haploinsuficiência , Canal de Sódio Disparado por Voltagem NAV1.2 , Animais , Camundongos , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Masculino , Feminino , Comportamento Animal , Aprendizagem , Recompensa , Tomada de Decisões , Humanos , Modelos Animais
15.
eNeuro ; 10(6)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37295945

RESUMO

Chronic nicotine results in dependence with withdrawal symptoms on discontinuation of use, through desensitization of nicotinic acetylcholine receptors and altered cholinergic neurotransmission. Nicotine withdrawal is associated with increased whole-brain functional connectivity and decreased network modularity; however, the role of cholinergic neurons in those changes is unknown. To identify the contribution of nicotinic receptors and cholinergic regions to changes in the functional network, we analyzed the contribution of the main cholinergic regions to brain-wide activation of the immediate early-gene Fos during withdrawal in male mice and correlated these changes with the expression of nicotinic receptor mRNA throughout the brain. We show that the main functional connectivity modules included the main long-range cholinergic regions, which were highly synchronized with the rest of the brain. However, despite this hyperconnectivity, they were organized into two anticorrelated networks that were separated into basal forebrain-projecting and brainstem-thalamic-projecting cholinergic regions, validating a long-standing hypothesis of the organization of the brain cholinergic systems. Moreover, baseline (without nicotine) expression of Chrna2, Chrna3, Chrna10, and Chrnd mRNA of each brain region correlated with withdrawal-induced changes in Fos expression. Finally, by mining the Allen Brain mRNA expression database, we were able to identify 1755 gene candidates and three pathways (Sox2-Oct4-Nanog, JAK-STAT, and MeCP2-GABA) that may contribute to nicotine withdrawal-induced Fos expression. These results identify the dual contribution of the basal forebrain and brainstem-thalamic cholinergic systems to whole-brain functional connectivity during withdrawal; and identify nicotinic receptors and novel cellular pathways that may be critical for the transition to nicotine dependence.


Assuntos
Receptores Nicotínicos , Síndrome de Abstinência a Substâncias , Masculino , Camundongos , Animais , Nicotina/farmacologia , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Encéfalo/metabolismo , Colinérgicos , RNA Mensageiro , Receptores Colinérgicos/metabolismo
16.
bioRxiv ; 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37034602

RESUMO

Chronic nicotine results in dependence with withdrawal symptoms upon discontinuation of use, through desensitization of nicotinic acetylcholine receptors and altered cholinergic neurotransmission. Nicotine withdrawal is associated with increased whole-brain functional connectivity and decreased network modularity, however, the role of cholinergic neurons in those changes is unknown. To identify the contribution of nicotinic receptors and cholinergic regions to changes in the functional network, we analyzed the contribution of the main cholinergic regions to brain-wide activation of the immediate early-gene FOS during withdrawal in male mice and correlated these changes with the expression of nicotinic receptor mRNA throughout the brain. We show that the main functional connectivity modules included the main long-range cholinergic regions, which were highly synchronized with the rest of the brain. However, despite this hyperconnectivity they were organized into two anticorrelated networks that were separated into basal forebrain projecting and brainstem-thalamic projecting cholinergic regions, validating a long-standing hypothesis of the organization of the brain cholinergic systems. Moreover, baseline (without nicotine) expression of Chrna2 , Chrna3 , Chrna10 , and Chrnd mRNA of each brain region correlated with withdrawal-induced changes in FOS expression. Finally, by mining the Allen Brain mRNA expression database, we were able to identify 1755 gene candidates and three pathways (Sox2-Oct4-Nanog, JAK-STAT, and MeCP2-GABA) that may contribute to nicotine withdrawal-induced FOS expression. These results identify the dual contribution of the basal forebrain and brainstem-thalamic cholinergic systems to whole-brain functional connectivity during withdrawal; and identify nicotinic receptors and novel cellular pathways that may be critical for the transition to nicotine dependence. Significance Statement: Discontinuation of nicotine use in dependent users is associated with increased whole-brain activation and functional connectivity and leads to withdrawal symptoms. Here we investigated the contribution of the nicotinic cholinergic receptors and main cholinergic projecting brain areas in the whole-brain changes associated with withdrawal. This not only allowed us to visualize and confirm the previously described duality of the cholinergic brain system using this novel methodology, but also identify nicotinic receptors together with 1751 other genes that contribute, and could thus be targets for treatments against, nicotine withdrawal and dependence.

17.
bioRxiv ; 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37502881

RESUMO

Norepinephrine (NE), a neuromodulator released by locus coeruleus neurons throughout cortex, influences arousal and learning through extra-synaptic vesicle exocytosis. While NE within cortical regions has been viewed as a homogenous field, recent studies have demonstrated heterogeneous axonal dynamics and advances in GPCR-based fluorescent sensors permit direct observation of the local dynamics of NE at cellular scale. To investigate how the spatiotemporal dynamics of NE release in the PFC affect neuronal firing, we employed in-vivo two-photon imaging of layer 2/3 of PFC in order to observe fine-scale neuronal calcium and NE dynamics concurrently. We found that local and global NE fields can decouple from one another, providing a substrate for local NE spatiotemporal activity patterns. Optic flow analysis revealed putative release and reuptake events which can occur at the same location, albeit at different times, indicating the potential to create a heterogeneous NE field. Utilizing generalized linear models, we demonstrated that cellular Ca2+ fluctuations are influenced by both the local and global NE field. However, during periods of local/global NE field decoupling, the local field drives cell firing dynamics rather than the global field. These findings underscore the significance of localized, phasic NE fluctuations for structuring cell firing, which may provide local neuromodulatory control of cortical activity.

18.
Neuropsychopharmacology ; 48(9): 1257-1266, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37015972

RESUMO

Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase clinical studies. However, relatively little is known about the behavioral and neural mechanisms of 5-MeO-DMT, particularly the durability of its long-term effects. Here we characterized the effects of 5-MeO-DMT on innate behaviors and dendritic architecture in mice. We showed that 5-MeO-DMT induces a dose-dependent increase in head-twitch response that is shorter in duration than that induced by psilocybin at all doses tested. 5-MeO-DMT also substantially suppresses social ultrasonic vocalizations produced during mating behavior. 5-MeO-DMT produces long-lasting increases in dendritic spine density in the mouse medial frontal cortex that are driven by an elevated rate of spine formation. However, unlike psilocybin, 5-MeO-DMT did not affect the size of dendritic spines. These data provide insights into the behavioral and neural consequences underlying the action of 5-MeO-DMT and highlight similarities and differences with those of psilocybin.


Assuntos
Alucinógenos , Transtornos Mentais , Camundongos , Animais , Psilocibina , Instinto , Metoxidimetiltriptaminas/farmacologia , Transtornos Mentais/tratamento farmacológico
19.
Curr Biol ; 32(2): R63-R67, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35077687

RESUMO

Psychedelics are compounds that alter consciousness by acting on serotonin receptors in the brain. The term 'psychedelic', from the Greek for mind manifesting, refers to the drugs' subjective effects and was first proposed by Humphry Osmond in 1956. Other terms have been used to emphasize different aspects of the psychological experiences produced by various related compounds, including hallucinogens (perceptual), entheogens (spiritual), and empathogens or entactogens (social/emotional). The diversity in terminology reflects the existence of hundreds of potential psychedelic compounds with a spectrum of behavioral and neurobiological effects. Recent data on the effectiveness of psychedelics for treating mental illnesses has led to a resurgence of interest in their neurobiological effects. The purpose of this Primer is to provide those interested in the field of psychedelics with a concise and accessible overview of the scientific data.


Assuntos
Alucinógenos , Transtornos Mentais , Encéfalo , Estado de Consciência , Alucinógenos/farmacologia , Alucinógenos/uso terapêutico , Humanos , Transtornos Mentais/tratamento farmacológico , Neurobiologia
20.
eNeuro ; 9(2)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35168951

RESUMO

In a competitive game involving an animal and an opponent, the outcome is contingent on the choices of both players. To succeed, the animal must continually adapt to competitive pressure, or else risk being exploited and lose out on rewards. In this study, we demonstrate that head-fixed male mice can be trained to play the iterative competitive game "matching pennies" against a virtual computer opponent. We find that the animals' performance is well described by a hybrid computational model that includes Q-learning and choice kernels. Comparing between matching pennies and a non-competitive two-armed bandit task, we show that the tasks encourage animals to operate at different regimes of reinforcement learning. To understand the involvement of neuromodulatory mechanisms, we measure fluctuations in pupil size and use multiple linear regression to relate the trial-by-trial transient pupil responses to decision-related variables. The analysis reveals that pupil responses are modulated by observable variables, including choice and outcome, as well as latent variables for value updating, but not action selection. Collectively, these results establish a paradigm for studying competitive decision-making in head-fixed mice and provide insights into the role of arousal-linked neuromodulation in the decision process.


Assuntos
Tomada de Decisões , Pupila , Animais , Tomada de Decisões/fisiologia , Aprendizagem/fisiologia , Masculino , Camundongos , Pupila/fisiologia , Reforço Psicológico , Recompensa
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