scholarly journals Central amygdala circuits modulate food consumption through a positive valence mechanism

2017 ◽  
Author(s):  
Amelia M. Douglass ◽  
Hakan Kucukdereli ◽  
Marion Ponserre ◽  
Milica Markovic ◽  
Jan Gründemann ◽  
...  
Keyword(s):  
Food Consumption ◽  
Positive Reinforcement ◽  
Serotonin Receptor ◽  
Brain Regions ◽  
Central Nucleus ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
Neuronal Mechanisms ◽  
Positive Valence

SummaryThe complex behaviors underlying the pursuit and consumption of rewards are integral to an organism’s survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is not well understood. The central nucleus of the amygdala (CeA) is implicated in feeding and reward behavior, but the specific neural players and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we define the neuronal mechanisms by which the CeA promotes consumption of food. We show, using in vivo activity manipulations and Ca2+ imaging, that CeA GABAergic neurons expressing the serotonin receptor 2a (Htr2a) modulate food consumption in multiple contexts, promote positive reinforcement and are active in vivo during eating. We demonstrate using electrophysiology, anatomical tracing methods and in vivo optogenetics that both intra-CeA and long-range circuit mechanisms underlie these functional effects. Finally, we show that CeAHtr2a neurons are poised to regulate food consumption through inputs from feeding-relevant brain regions. Our study highlights a mechanism by which defined CeA neural circuits positively regulate food consumption.

scholarly journals Synaptic plasticity in the mesolimbic dopamine system

2003 ◽  
Vol 358 (1432) ◽  
pp. 815-819 ◽  
Author(s):  
Mark J. Thomas ◽  
Robert C. Malenka
Keyword(s):  
Synaptic Plasticity ◽  
Drugs Of Abuse ◽  
Neural Circuit ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Mesolimbic Dopamine ◽  
Dopamine System ◽  
Mesolimbic Dopamine System

Long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical mechanisms that contribute to the neural circuit modifications that mediate all forms of experience-dependent plasticity. It has, however, been difficult to demonstrate directly that experience causes long-lasting changes in synaptic strength and that these mediate changes in behaviour. To address these potential functional roles of LTP and LTD, we have taken advantage of the powerful in vivo effects of drugs of abuse that exert their behavioural effects in large part by acting in the nucleus accumbens (NAc) and ventral tegmental area (VTA); the two major components of the mesolimbic dopamine system. Our studies suggest that in vivo drugs of abuse such as cocaine cause long-lasting changes at excitatory synapses in the NAc and VTA owing to activation of the mechanisms that underlie LTP and LTD in these structures. Thus, administration of drugs of abuse provides a distinctive model for further investigating the mechanisms and functions of synaptic plasticity in brain regions that play important roles in the control of motivated behaviour, and one with considerable practical implications.

Naltrexone administered to central nucleus of amygdala or PVN: neural dissociation of diet and energy

2000 ◽  
Vol 279 (1) ◽  
pp. R86-R92 ◽  
Author(s):  
Michael J. Glass ◽  
Charles J. Billington ◽  
Allen S. Levine
Keyword(s):  
Food Intake ◽  
Food Consumption ◽  
Neural Circuitry ◽  
Brain Regions ◽  
Wide Distribution ◽  
Central Nucleus ◽  
Total Energy Consumption ◽  
Direct Stimulation ◽  
The Central Nervous System ◽  
Diet Intake

There is evidence that opioids may affect food consumption through mechanisms as diverse as reward or energy metabolism. However, these hypotheses are derived from studies employing peripheral or, more rarely, intracerebroventricular administration of drugs. Opioid receptors have a wide distribution in the central nervous system and include a number of regions implicated in food intake such as the hypothalamic paraventricular nucleus (PVN) and the central nucleus of the amygdala (ACe). It is not known whether local opioid receptor blockade in either of these regions will produce similar effects on food intake. To examine this issue, a chronic cannula was aimed at either the PVN or ACe of rats that were fed a choice of a high-fat and high-carbohydrate diet, which allows for the measurement of both preference and total energy consumption. Naltrexone influenced preferred and nonpreferred food consumption, depending on the site of administration. Consumption of both preferred and nonpreferred diets was suppressed after PVN naltrexone administration, whereas only preferred diet intake was reduced after ACe injection of naltrexone. The present evidence indicates that direct stimulation of different brain regions with naltrexone may be associated with diverse effects on diet selection, which may be accounted for by manipulation of specific functional neural circuitry.

scholarly journals Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

2021 ◽  
Vol 22 (4) ◽  
pp. 1666
Author(s):  
Francesco Traccis ◽  
Valeria Serra ◽  
Claudia Sagheddu ◽  
Mauro Congiu ◽  
Pierluigi Saba ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Female Offspring ◽  
Dopamine Neurons ◽  
Male Rat ◽  
Dependent Manner ◽  
Mesolimbic Dopamine ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
The Impact

Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase in dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.

scholarly journals Hunger neurons drive feeding through a sustained, positive reinforcement signal

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yiming Chen ◽  
Yen-Chu Lin ◽  
Christopher A Zimmerman ◽  
Rachel A Essner ◽  
Zachary A Knight
Keyword(s):  
Positive Reinforcement ◽  
Neural Mechanisms ◽  
Energy Deficit ◽  
Neuron Activity ◽  
Optogenetic Stimulation ◽  
Neuron Activation ◽  
Positive Valence ◽  
Stimulation Of ◽  
Hunger Drive

The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states.

scholarly journals 2181 Age-related change in 5-HT6 receptor availability in healthy male volunteers measured with 11C-GSK215083 PET

2018 ◽  
Vol 2 (S1) ◽  
pp. 3-4
Author(s):  
Rajiv Radhakrishnan ◽  
Nabeel Nabulsi ◽  
Edward Gaiser ◽  
Jean-Dominique Gallezot ◽  
Shannan Henry ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Serotonin Receptor ◽  
Brain Regions ◽  
Healthy Male ◽  
Time Activity ◽  
Age Related ◽  
Study Population ◽  
Cortical Regions ◽  
Age Range

OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.

scholarly journals Prenatal THC does not affect female mesolimbic dopaminergic system in preadolescent rats

2020 ◽  
Author(s):  
Francesco Traccis ◽  
Valeria Serra ◽  
Claudia Sagheddu ◽  
Mauro Congiu ◽  
Pierluigi Saba ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Female Offspring ◽  
Dopamine Neurons ◽  
Male Rat ◽  
List Type ◽  
Dependent Manner ◽  
Mesolimbic Dopamine ◽  
Dopamine System ◽  
Mesolimbic Dopamine System

AbstractCannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes towards it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase of dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related-behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.HighlightsPCE female offspring do not manifest a disease-relevant phenotypePrenatal THC does not affect female dopaminergic neuronsPCE female mesolimbic dopamine function is less responsive to acute THC

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

Sign in / Sign up

Export Citation Format

Share Document