@article {46574, title = {Neurons for hunger and thirst transmit a negative-valence teaching signal.}, journal = {Nature}, volume = {521}, year = {2015}, month = {2015 Apr 27}, pages = {180-5}, abstract = {

Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics of two separate neuron populations that regulate energy and fluid homeostasis by using cell-type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis.

}, doi = {10.1038/nature14416}, author = {Betley, J Nicholas and Xu, Shengjin and Cao, Zhen Fang Huang and Gong, Rong and Magnus, Christopher J and Yu, Yang and Sternson, Scott M} } @article {6417, title = {Neural circuits and motivational processes for hunger.}, journal = {Current Opinion in Neurobiology}, volume = {23}, year = {2013}, month = {2013 Jun}, pages = {353-60}, abstract = {

How does an organism{\textquoteright}s internal state direct its actions? At one moment an animal forages for food with acrobatic feats such as tree climbing and jumping between branches. At another time, it travels along the ground to find water or a mate, exposing itself to predators along the way. These behaviors are costly in terms of energy or physical risk, and the likelihood of performing one set of actions relative to another is strongly modulated by internal state. For example, an animal in energy deficit searches for food and a dehydrated animal looks for water. The crosstalk between physiological state and motivational processes influences behavioral intensity and intent, but the underlying neural circuits are poorly understood. Molecular genetics along with optogenetic and pharmacogenetic tools for perturbing neuron function have enabled cell type-selective dissection of circuits that mediate behavioral responses to physiological state changes. Here, we review recent progress into neural circuit analysis of hunger in the mouse by focusing on a starvation-sensitive neuron population in the hypothalamus that is sufficient to promote voracious eating. We also consider research into the motivational processes that are thought to underlie hunger in order to outline considerations for bridging the gap between homeostatic and motivational neural circuits.

}, issn = {1873-6882}, doi = {10.1016/j.conb.2013.04.006}, author = {Sternson, Scott M and Betley, J Nicholas and Cao, Zhen Fang Huang} } @article {6672, title = {Parallel, redundant circuit organization for homeostatic control of feeding behavior.}, journal = {Cell}, volume = {155}, year = {2013}, month = {2013 Dec 5}, pages = {1337-50}, abstract = {

Neural circuits for essential natural behaviors are shaped by selective pressure to coordinate reliable execution of flexible goal-directed actions. However, the structural and functional organization of survival-oriented circuits is poorly understood due to exceptionally complex neuroanatomy. This is exemplified by AGRP neurons, which are a molecularly defined population that is sufficient to rapidly coordinate voracious food seeking and consumption behaviors. Here, we use cell-type-specific techniques for neural circuit manipulation and projection-specific anatomical analysis to examine the organization of this critical homeostatic circuit that regulates feeding. We show that AGRP neuronal circuits use a segregated, parallel, and redundant output configuration. AGRP neuron axon projections that target different brain regions originate from distinct subpopulations, several of which are sufficient to independently evoke feeding. The concerted anatomical and functional analysis of AGRP neuron projection populations reveals a constellation of core forebrain nodes, which are part of an extended circuit that mediates feeding behavior.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2013.11.002}, author = {Betley, J Nicholas and Cao, Zhen Fang Huang and Ritola, Kimberly D and Sternson, Scott M} } @article {6488, title = {Optogenetics: potentials for addiction research.}, journal = {Addiction Biology}, volume = {16}, year = {2011}, month = {2011 Oct}, pages = {519-31}, abstract = {

Research on the biology of addiction has advanced significantly over the last 50 years expanding our understanding of the brain mechanisms underlying reward, reinforcement and craving. Novel experimental approaches and techniques have provided an ever increasing armory of tools to dissect behavioral processes, neural networks and molecular mechanisms. The ultimate goal is to reintegrate this knowledge into a coherent, mechanistic framework of addiction to help identify new treatment. This can be greatly facilitated by using tools that allow, with great spatial and temporal specificity, to link molecular changes with altered activation of neural circuits and behavior. Such specificity can now be achieved by using optogenetic tools. Our review describes the general principles of optogenetics and its use to understand the links between neural activity and behavior. We also provide an overview of recent studies using optogenetic tools in addiction and consider some outstanding questions of addiction research that are particularly amenable for optogenetic approaches.

}, keywords = {Animals, Brain, Dopamine, Gene Expression, Genetic Techniques, Humans, Light, Nerve Net, Nerve Tissue Proteins, Neurons, Neurosciences, Optical Tweezers, Rhodopsin, Substance-Related Disorders, Translational Medical Research, Voltage-Sensitive Dye Imaging}, issn = {1369-1600}, doi = {10.1111/j.1369-1600.2011.00386.x}, author = {Cao, Zhen Fang Huang and Burdakov, Denis and Sarnyai, Zolt{\'a}n} }