Research Projects
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Hedonic hotspots of 'Liking' -- The brain's pleasure gloss

Pleasure arises within the brain. Sweetness or other natural pleasures are mere sensations as they enter the brain, and brain systems must actively paint the pleasure onto sensation to generate a 'liking' reaction -- as a sort of pleasure gloss or varnish. Our lab has discovered brain generators of sensory pleasure, in the form of anatomical 'hedonic hotspots' in the brain, which use neurochemcal signals paint intense pleasure on sensation, embedded within larger hedonic circuits. It is important to identify such pleasure-causing brain hedonic hotspots, neurochemicals and circuits, in order to identify true mechanisms of pleasure. The need to find true pleasure generators is especially pressing because hedonic circuit dysfunctions may underlie mood disorders and related clinical disorders, and because several other brain candidates once thought to mediate pleasure are now increasingly recognized to not cause pleasure after all (e.g., dopamine, electrical brain stimulation). Therefore we aim to find true causes and mechanisms in the brain for pleasure. [General review papers on pleasure 'liking': ]

The hedonic hotspots that generate pleasure 'liking' are each about a cubic millimeter in size (in rats; perhaps a cubic centimeter in you), and contained in limbic forebrain structures such as the nucleus accumbens and the ventral pallidum. In hotspots the hedonic gloss is painted by brain chemicals such as mu opioids and endocannabinoids, which are natural brain versions of heroin and marijuana that amplify a sensory pleasure. If we activate those neurochemical receptors (via painless microinjection of tiny droplets of drug directly into a hedonic hotspot) we increase the 'liking' reactions elicited by sweetness. [Research examples]

Using microinjections and lasers to activate the brain. For drug microinjections, we have developed a Fos plume mapping technique to more precisely map the hedonic hotspots (and chemical pleasure paints) when drug microinjections amplify 'liking'. Similarly we are now using laser pulses of light to activate hotspots via optogenetics techniques in which a desired neural system is targeted by a virus microinjection that makes it develop photoreceptors and become activated by light (photo of brain illuminated by optic fiber that transmits laser).

We have also studied how pleasure is coded by the firing patterns of neurons within those hotspots, similar to a brain Morse code for 'liking', in collaboration with the Aldridge lab . Our goal is to better understand how brain hedonic hotspots act together in an integrated hedonic circuit to mediate 'liking' for sensory pleasures.

'Wanting' - Incentive Salience
How does reward 'wanting' differ from reward 'liking'? A common brain myth is that dopamine mediates sensory pleasure, but our research has helped indicate that dopamine mediates only a form of ''wanting' for reward called incentive salience, and not pleasure 'liking'. Our goal is to better understand the psychological nature of incentive salience and to clarify its brain mesolimbic mechanisms. We are currently studying how brain circuits converge current motivation with prior learning to focus 'wanting' on particular targets, relevant to why addicts 'want' mostly drugs whereas binge eaters 'want' mostly food . To study neural substrates of 'wanting', we use psychological and neurobiological techniques that isolate incentive salience from other psychological functions such as reinforcement learning or pleasure 'liking'. Our measures inclued cue-triggered 'wanting' ( based on Pavlovian-instrumental transfer), and 'motivational magnet' features of reward cues ( based on autoshaping). Some of our studies involve collaboration on hyperdopaminergic DAT-knockdown mutant mice (with Xiaoxi Zhuang at U. Chicago), and on limbic neuronal coding (with J. Wayne Aldridge ). Sensitization of 'wanting' may be an important component of irrational desires such as addiction .

(; 'Wanting' overview 1 ).

Desire versus dread in in limbic nucleus accumbens
What determines if something is nice or nasty? Does desire share anything in common with fear? We have found neural affective building blocks that generate both desire and dread, embedded in a limbic keyboard or brain map of affective valence (positive versus negative emotion organinzed in rostrocaudal gradients) in the nucleus accumbens . Affective building blocks may also include hidden incentive components inside stress, such as CRF mechanisms that act in nucleus accumbens to amplify incentive 'wanting'. This may contribute to the ability of stress to precipitate binges of compulsive consumption. See a natural 'rodent dread' behavior exploited by our affective neuroscience studies (antipredator defensive burying):

. Addictive drugs can cause permanent neural sensitization in brain mesolimbic systems of incentive salience. Sensitized incentive salience means addicts have compulsive 'wanting' to take drugs, which can last months or years. Much evidence has emerged to favor this idea in the decade since Terry Robinson and Berridge first proposed it, and it continues to influence current neuroscience research . We stress Incentive-Sensitization theory does not provide a cure for addiction, but it does help pinpoint a crucial aspect of what goes wrong.

Eating disorders and Food Addiction: Another aapplication is binge eating and obesity and related disorders that might involve food 'liking'/'wanting' mechanisms ) .