Open neuroscience talk at the University of Sussex next Wednesday - by me :)

I've been asked to give a talk to the Artificial Life Reading Group (Alergic) at the University of Sussex next Wednesday (Oct 6). I'm gonna take the opportunity to articulate my understanding of brains as spiking attractor networks that seek operant control through dopamine-mediated reward learning. This is actually a simple mix of old ideas, but my model system - the buccal ganglia - and experimental technique - the multielectrode array - allows me to quantify and visualize the various components of the theory. I'll also have the opportunity to test some new thoughts on brain-computer interfacing.

Network dynamics, dopamine and operant control: lessons from the molluskan buccal ganglia

Time: Oct 6, 16:30-18:00

Abstract

Multielectrode array (MEA) analysis of molluskan nervous systems is an experimental technique recently developed at the University of Sussex (Harris et al., 2010). Here I discuss our current understanding of the molluskan buccal ganglia, with examples from the MEA work, and relate it to more general theories of network dynamics, pattern generation, dopamine-mediated reward and operant control. Variance in the neural pattern for feeding behaviour, which the buccal ganglia continue to generate in vitro, allows the brain to search for optimal feeding strategies in changing environments (Brezina et al., 2006) and can be considered a rudimentary form of free will (Brembs, in press). I argue that this ability to generate variable, reward-sensitive motor output is a central function of brains, and discuss experimental and computational approaches toward a better understanding of it.

References: Brembs (in press) Proc of the Royal Soc; Harris et al (2010) J Neurosci Methods 186(2):171-8; Brezina et al (2006) Neurocomputing 69(10-12):1120-1124.

The talk will be recorded and will hopefully be available on the iPlant channel in a few weeks but please get in touch if you are in the UK and would like to attend the talk (and the enjoyable post-talk discussion in the bar). RSVP on Facebook here.

Spontaneous and dopamine-driven brain activity

Last weekend I started working on a video aimed at giving viewers a feel for the beauty and complexity of the network activity we record in the lab (see this entry for details). The trigger for this was meeting a friend who was able to create for me the Java code necessary to run the spike rate data through JFugue. My own attempts at this had not been completely successful. Simultaneously, Björn Brembs started posting a series of excellent and quite closely related videos over on his YouTube channel, which kept me motivated (also, being able to point to videos from Bill Kristan's lab certainly helped convince my supervisors of the wisdom of the idea).

There will be more of these, at least I intend for there to be, because it was a lot of fun to make and there are a range of variations and improvements on the audiovisual presentation to explore, as well as a whole bunch of specific topics I'd like to address. But for now, this is it.

Drifting

You're on a train, staring out the window at power lines, green planes and sky. Your mind wanders. You think of things that happened years ago, people still important in your life. You recall an exchange, you relive the feel of it; embarrassment, adoration, indifference, adventure, but context-dependent and with a specific, complex taste; you're watching rows of hedges, trees and sheep flash by, but in your mind's eye you see streets, places, a room where years ago someone close to you slept. The room most likely remains but you know nothing of the persons living there now; they never enter your mind in any way, why should they? Your friend lives elsewhere now, lives where the train is heading. For three hundred and thirty two seconds your brain attracts around those memories - the room, the bathroom, food and conversations you had there, films you watched - then stops, and you snap out of it, reach for your bottled water, and reconnect with your surroundings; with the people moving or sitting still around you. You don't know why your mind drifted to those particular memories, or what made it stop suddenly - or rather, you DO know, about quasi-stable patterns of brain activity, maintained by dopamine and obvious given your destination - but why that PARTICULAR chain of thoughts and memories, and why the sudden stop? You imagine the dyanmics of your brain, imagine a brain-shaped animation of swirling electrical potential, action potentials, ever-changing, save for brief periods where stable configurations are reached that attract the swirling mass around a recognizable shape, a place, a thought, a memory, before loosing interest and drifting off. You look around again, search the environment for stability, attraction, dopamine. The woman next to you in black, with the clean features, the headphones, the short hair and the eyebrows. The landscape outside, darker now; houses, horses, a town. There's nothing there to keep you, and your mind begins to drift again. It makes you sad, restless, and you put the music back on.

27 January 2010

Dear readers, I'm acutely aware that my blog has stagnated. I blame FriendFeed and Facebook, where people actually INTERACT with my links and loose thoughts, but the real reason is simply contentment: life is going well at the moment, all things considered, and so I have nothing to say, no tensions to sublimate or at least whine about. Fear not though, I intend to create NEW TENSIONS by having an ABSOLUTELY ALCOHOL-FREE FEBRUARY!

In the meantime, here is the original version of a column I wrote, which, after some peculiar mangling by the editors, was recently published in the local student paper. Readers of this blog will find the text annoyingly simplistic, or at least old hat; I post it here simply to stress that I would never - ever - make such use of question- and exclamation-marks.

The most important thing in life
Christopher Harris

What fascinates me most about the brain is its motivation, the fact that it wants and desires. I'm also acutely aware of the limits of my own free will: eat less, exercise more, study more, be more social, dare to do this, stop doing that; it's like a never-ending struggle with my own will, and I know I'm not the only one frustrated by this experience, especially now, with new year's resolutions failing left and right. So what's going on?

In the middle of your brain you have half a million neurons that release dopamine into your frontal lobes. These neurons form the core of your brain's reward system, which generates your motivation. Rewards, like food, drink, play, sex and addictive drugs, raise dopamine concentrations in your brain, as do learned rewards like money. Unexpected rewards are particularly effective, and dopamine builds up in anticipation of uncertain rewards, making everyone at the bus stop stare at the bend where the bus will appear. Low dopamine concentrations on the other hand make you distracted and disinterested.



Different behaviours are produced by different groups of neurons in the frontal lobes. These neuronal groups run on dopamine, and so the behaviour you feel most motivated to perform at any given moment is that of the group that generates the most dopamine. Eating sweets is easy: with a few simple muscle movements it activates your dopamine neurons through your taste buds. Studying for a distant exam is hard: it requires your full attention and activates your dopamine neurons only indirectly, through your prefrontal cortex, which simultaneously has to inhibit more immediate urges like surfing the web, going out or watching a film. You may have heard of Phineas Gage, who destroyed his prefrontal cortex in an accident and lost his impulse control and his ability to follow plans for the future.

New year's resolutions fail because we make them considering only the wonderful goal, which by itself produces plenty of dopamine, especially when it's new and feels like a fresh start. We don't realize how hard it will be for our prefrontal cortices to provide the new neuronal groups with enough dopamine to make us runregularly, or read in the library, or go to the gym, or in any way compete with the entrenched neuronal groups that have us sit on the couch, or over-eat, or smoke. On a normal day, the further away a goal is, the less attractive it seems, because the further away a reward is, the less dopamine it generates. So the trick to keeping new year's resolutions: be nice to your prefrontal cortex.

There's more to motivation of course, the reward system is enormously complex. This is how I like to think about it though, and it's worked so far. It helped me quit smoking, knowing that the urge was strong because dopamine neurons are covered in nicotine receptors, but that the brain would 'forget' this in a few months and the urge would go away. It helps me understand all kinds of thoughts, habits, excitements and hang-ups. It helps me understand my own brain. Check in next week for another bit of this story, and join the dopamine fan page on Facebook for references and more information.

See you February.

iPlant fiction - Chapter 3

This is the third chapter of my novel-in-progress. This and previous chapters are available on the main website.

- "Every time, every time we meet she's late"
Lucy and Ike stood waiting outside D's assistant's office. The glass door was shut and the room inside in semi-darkness. The assistant was almost twenty minutes late.
- "Dopamine deficiency, swear to God", Lucy said.
- "Which one?", Ike said.
- "Midbrain insufficiency. Plain cell numbers, not enough dopamine."
- "Not a receptor problem? D1, D2? Unresponsive adrenal glands?"
- "Adrenal problems don't cause chronic lateness, she relies on her adrenal stress response to get her ass off the couch in the morning, but that doesn't kick in until she's critically late and then there's terrible traffic or some shit and we end up loosing our fucking morning staring at her door.."
- "Never heard you curse before", Ike said.
- "Period", Lucy said, holding her elbow and stepping restlessly on the spot.
- "D1 then? D2? Receptors not growing the way they should?"
- "Midbrain insufficiency"
- "How do you know? How would you know without scanning her? You got her scans??"
- "No. I just know."
- "Bullshit"
- "Fuck you"
They glared at each other for a brief moment.
"It's not D1", Lucy said, "because she's not inattentive and certainly not impulsive. And it's not D2 because she's a vicious learner, not just memoranda but procedure as well, that's why D hired her."
- "When was that?"
- "Same as me, for a while I thought we'd work together - her background is biotech and biomedical patents - but she's all administration now and real close to D."
- "Balanced D1 and D2 deficienciencies then? Hyperactive dopamine transporter?"
- "Knew you'd say that"
- "Well?"
- "You're pretty obvious Ike, as a person"
- "You're stalling"
- "Midbrain insufficiency. Not enough dopamine neurons."
- "How could you possibly know that without looking at her scans?!"
- "Calm down", Lucy said and lowered her voice as a small group of people emerged from the elevator at the end of the corridor and disappeared around a corner. "Look, first of all Meg and I agree on it and that's rare and I trust her judgement when it comes to guessing phenotypes and so should you. Second, Marlena is unstable, not in a way that really impacts her work but she's selectively anhedonic, severely - sometimes she truly doesn't see the point or doesn't care unless she's told and I bet you she's a lot less polished at home. But it's a partial problem and if you don't look for it you might not notice: and that's the point, receptor deficiencies have a smooth psychological profile, transporter deficiencies doubly so. Marlena's problem comes in patches. Third, look at her forehead! I'm not saying she's got a small midbrain, I'm saying her forebrain is oversized and sometimes she doesn't have the dopamine to keep all her units running, especially in the morning, which is why we're standing here wasting time."
Ike watched her speak.
- "Don't you ever tell anyone what I just said", Lucy said and suddenly looked nervous.
- "Course not"
- "I shouldn't have said all that"
- "I'm not telling, why would I tell?"
- "Shouldn't have said that"
- "Look, we're not gonna work well together if you keep distrusting me"
- "'Keep'?"
Ike paused, unsure.
- "Meg", he said finally, "You're trying to protect her from me"
Lucy burst into a high laugh.
- "Don't wanna sound cliché or theatrical but I'm more concerned about what she'll do to you, if you step on her feet. Do whatever you want, just don't fuck up so you can't work together."
- "How about some pointers then? What do you mean 'what she'll do' to me? She 'unstable' too?"
- "Oh no, I've gossiped more than enough"
They were silent for a while.
- "How about you tell me something?", Lucy said after a while, "How about you tell me where you got that scar?" She stroked the left side of her jaw, indicating a thick scar on his.
- "Stepped on someone's feet", Ike mumbled.
Marlena suddenly appeared from the elevator at the end of the hallway and hurried towards them.
- "I'm so sorry I'm late", she said, "Traffic's terrible and it's raining. Please come along."
Lucy and Ike looked with surprise at eachother as they followed Marlena down the corridor towards D's office, which she opened with a metal key.
- "We need Ike fully installed by the end of the day", Marlena said. She sat down behind D's large black desk, roused his computer with a quick mouse shake, typed out a long string of characters and hit enter unnecessarily hard. The computer logged in, showing the company logo against a dark background. She gestured for them to sit down in two easy chairs opposite the desk. "Water?" She fished up a bottle of sparkling mineral water from a drawer.
- "No thanks", they both said, attentive.
Marlena paused and looked at them.
- "You've been hired", she finally said to Ike, "I thought you knew."
Ike beamed.
- "D wants you installed and ready to work by the end of the day, you're going with the others to Brussels tomorrow."
- "That's excellent!", Ike exclaimed.
- "You need to bring your scans, we need you to discuss them with some people from the council"
There was a pause.
- "The brain scans", Marlena continued, looking steadily at him "You and Chris used his new ligands to make scans of your brain. You imaged your serotonin system a week ago in the PET scanner. You found substantial changes."
- "Chris told you?", Ike said, "He told D? He said I'd get him fired if I told anyone. So did you.", he turned to Lucy.
- "I don't know anything about this", Lucy said and held up her hands "don't particularly want to know"
- "You're going to Brussels to determine the council's true limits on experimental and commercial deep brain stimulation", Marlena said, "You want to work here because, one day, you want to undergo such surgery yourself - sooner rather than later I understand"
- "I want an iPlant", Ike said.
- "The iPlant is a theoretical construct as far as human application is concerned", Marlena said. "We need a battery of permissions and suspicions cleared before we can proceed with surgery. You're going to Brussels to test the European medical law authorities on that particular point. You'll pursue the argument that our implants and surgical procedure are worth the risks of surgery to customers who have never been hospitalized but who might nevertheless consider themselves neurologically handicapped. Your scans will provide a vivid example of such a case."
- "Do we really want to use one unauthorized procedure to get permission for another?", Lucy asked.
- "You're not going there to get permisison, just to test the waters..", Marlena began.
- "I know", Lucy said, "And to be frank we'll probably proceed with the iPlant either way. I'm asking whether these scans might do more harm than good."
- "D tells me they are quite convincing", Marlena said and looked at Ike.
The three fell silent for a moment.
- "Jeez Ike", Lucy finally said, "How much ecstasy did you have?"
- "It makes sense", Ike said, "I'm in"
- "Brilliant", Marlena said and began filling out a form she'd pulled up on the screen.
- "How much did you have?", Lucy asked again.
- "Enough", Ike said.
- "If you'll come with me over here..", Marlena said and led Ike over to an eye and finger-scanner beside a small safe in the far corner of the room, next to a large liquor cabinet. "Just place your fingertips here please.. and look at the white dot there.. and again.. excellent."

Dopamine, attention, working memory, neuronal groups and the prefrontal cortex

YouTube video messed up, use this one http://www.facebook.com/video/video.php?v=591916852334

How bad do you want it? (update 1)

Deep brain stimulation (DBS) electrodes offer a window into regions of the human brain that would otherwise, for obvious ethical reasons, not be available for scientific analysis. Interesting activity related to sensation, cognition and behavior can, for example, be recorded from DBS electrodes placed in the subthalamic nucleus for the purpose of treating Parkinson's disease (e.g. Balaz et al 2008, Bronte-Stewart et al 2009).

More and more, DBS is being applied to the human reward circuit to treat obsessive-compulsive disorder and depression (see previous blog post). Specifically, the nucleus accumbens (ventral striatum) is being targeted. Dopamine release into the nucleus accumbens is the strongest reward-signal we know of; it is core to the generation of motivation and learning.

So, what will we see when we start recording from DBS electrodes placed in the human nucleus accumbens? I'll bet my boots that we'll be able to detect changes in dopamine release and reward-processing with MUCH higher precision than when we use brain scanners. Averaged over many trials and patients, recordings like that could allow us to quantify the reward value of things in the world, and relate the activity of the human reward circuit not just to sensation but also to cognition and behavior.






← Monkey reward circuit neurons respond to a liquid reward. How exactly would the human reward circuit respond to a liquid reward? Or an invitation to a BBQ? Or two political candidates? Or heroin? Or boredom? Or praise? Or coffee? Or any of the various reinforcers that shape our behaviour, thoughts and feelings? I think we're about to find out.



Edit: publications exploring this line of research are already available: Münte et al 2008, Cohen et al 2009, Zaghloul et al 2009, Cohen et al 2008.

Why it's hard to stop smoking

Dopamine and the frontal lobes

What is dopamine?

This is a first draft, I need a better microphone and I'm not sure about the text. Any constructive criticism?

Transcript: Dopamine is a very important chemical that regulates thought, movement, attention, motivation and learning. It's synthesized by neurons in the middle of the brain but is released all over, in small and large doses.

In small doses, it activates D2 receptors, which reinforces ongoing thoughts and movements. If you're eating pizza, the pleasant taste will activate dopamine neurons, raise dopamine concentrations in your brain, and you'll feel motivated and keep on eating. If you're experiencing something new or expecting something good, dopamine levels can rise up to 100% and you feel excited and completely focused. Being unfocused and easily distracted means your brain is low on dopamine - that's why Ritalin, amphetamine and coffee helps people with attention deficit disorder concentrate.

When something important, unexpected or rewarding happens, large amounts of dopamine are released, which activate D1 receptors and stimulate learning and the formation of new connections between neurons. Memories and habits are formed this way. All addictive drugs release large amounts of dopamine in the brain, but so does good food and drink, and sex, social pleasure, and money.. everything you want releases dopamine, and you want it because it releases dopamine. Things are important and valuable only if they activate your dopamine neurons; if you're still watching this video it's because it's releasing dopamine; and whatever you do when this movie stops will be what releases most dopamine.

More on dopamine: http://www.iplant.eu/monoamine.html

Thoughts on forks

Whenever there is purposeful, goal-directed behavior going on, dopamine is involved. Without dopamine, there is no purposeful behavior. At 1% of normal dopamine concentrations even feeding and drinking stops. In Parkinson's disease the parts of the brain most intimately involved with purposeful movement (as opposed to thinking) are deprived of dopamine, and at 20% of normal concentrations it becomes hard to move. Dopamine is key to organized behavior and motivation: it reinforces activity in brain tissue and strengthens synapses.

So whenever you see purposeful behavior going on you might ask yourself "where is the dopamine coming from?". Only rarely do we see humans engaged in behavior that directly activates dopamine neurons. Eating comes to mind: sensory neurons in the mouth detect the presence of good food and immediately activate dopamine neurons in an attempt, if you will, to reinforce whatever behavior brought the food there. But that behavior, the movement of the fork or the chop-sticks, was learnt at some point. Suckling is the only form of eating we know from the start. We suckled the breast and the milk was warm and sweet and we stopped crying. We suckled the twig and it was cold and hard and we cried. When suckling brought warmth and sugar, dopamine was released and the neuronal ensembles generating the behavior and remembering the context were reinforced. Later we learned a bottle works almost as well. We learned to hold the bottle. And a few years and millions of dopaminergic learning experiences later we learned to use the fork.

Brainbeat

I'm standing on the vibrating, billowing hills of the tegmentum. Spherical and star-shaped cells; thin, sprawling nerve fibres; and thick, pulsating blood vessles stretch out in all directions. The ground is thick with receptors; twisting out of the bulging membranes like weeds and crystal algae.

The fluid is thick with glutamate; it envelops the cells, pulls on them, tears on their branches, and they willingly suck the salty fluid. Every few hundred milliseconds they trip eachother over the theshold, fluctuate, and generate a single, synchronized electrical impulse that shoots off along the medial forebrain bundle. It's a tonic, steady beat. Far away in the frontal lobe, that rhythm keeps the cortex active, keeps the thoughts alive, even in dreams.

234 151 dopamine neurons in this lobe. The cells are warm, depolarized, expectant; singing their neverending tonic song at three hertz, with more than usual synchrony. Pulse. Pulse. Pulse. Pulse. Pulse. Pulse. In the distance below, the dark substantia nigra cells warm up to the tune.

There. The steady rhythm is interrupted. The single expected nerve impulse is trippled. Pandemonium. The ground is trasformed as dopamine floods from neighbour to neighbour. Branches extend and reconnect. Entire cell bodies move as gap junctions synapse and pull cell membranes closer together. Again. Another tripplet. The background rhythm is up to four hertz now. Pulse. Pulse. Pulse pulse pulse. And then silence. A whole second passes before the tonic song is resumed and the cells begin to break rank and recover.

Something just happened.

Fluctuations

The interpretation of dreams

Yesterday I went to a lecture by Dr. Jim Hopkins, a former editor of MIND. The lecture was entitled Psychoanalysis, Dreams and Biosemantic Representation. I didn't expect my muse to be in the room, but Jim began the lecture by informing us that dopamine neurons resume normal, daytime-like activity during dreaming. Shock. Apparently dopamine neurons resume normal activity about once every hour during sleep, and this coincides with dreaming and the interruption of slow wave sleep. I've got no articles on it yet but it makes perfect sense: dopamine flow returns to the cortex, the slow rhythm pumping out of the thalamus is interrupted and the neruonal growth we call consciousness resumes. But it's a consciousness that is disconnected from sensory reality; unhinged; unreal; pure memory and imagination forming the dopaminergic narrative. Dreaming then, is just like waking life, a constant focus on that which generates most dopamine (see image below); but unrestrained and dissociated from the physical environment it lets us recombine and reevaluate our memories and aspirations. Jim tried to use the dopamine-reward connection to argue for the Freudian intepretation of dreams a wish fulfilment, but though dreams may share with waking-life a constant SEEKING, maybe they are better thought of simply as exploration: the blind, sleeping brain exploring itself, seeking the dopamine of fantasy and nightmare alike. Once a dopaminergic source has been found, the brain explores it, much like a day-dream, and a narrative is created. Dreaming is the cortical elaboration of a dopaminergic trace, in the chemical environment of a sleeping body, untethered by sensation, movement and the environment.



A month ago I wrote a few lines about endogenous activation of dopamine neurons. Here's an elaborated diagram. The frontal lobes are driven (SEEKING) to activate dopamine neurons, both directly and via their connections to the rest of the cortex. They can also use their connections to the motor cortex to make the eyes follow an attractive price, a strange animal or a threatening shadow, all of which would supply them with dopamine via other brain regions. They can go further into abstraction, plan ahead, and use their motor connections to orchestrate complex behaviors that eventually place the body in a situation where any (or all) of the other brain structures with direct connections to the dopamine neurons are stimulated (consider the things in red). This is will. But in dreaming, the frontal lobes have no access to the world, and must explore the dream using only their connections to the rest of the sleeping brain.

DA-5HT in 2D

Work in progress

The iPlant is all good and well but endogenous - natural - activation of midbrain dopamine (DA) neurons is just as important. DA neurons, whose function is strengthening of active cell assemblies in the frontal cortex ('attention'), generation of motivation ('desire'), and facilitation of declarative learning in the hippocampus and procedural learning in the striatum, are naturally activated by many nerve bundles, including glutamatergic (Glu) projections from sensory and frontal cortex. Of these two, the frontal cortex is more important, because it receives more DA and expresses more DA receptors, and therefore forms, with these DA neurons, an enormously adaptive and tightly knit circuit that we call 'I'.

In the addictive personality (ADHD humans, SH rats) the ability of the frontal cortex to activate and be activated by midbrain DA neurons is low, making the individual unusually reliant on sensory and other ways of activating midbrain DA neurons. Although a slim circuit and its steep delay of reinforcement gradient ('high impulsivity') may have been adaptive during evolution it can be a profound nuisance in a post-industrial environment that generally rewards long-term thinking and self-discipline. Recieving relatively little dopamine, the frontal cortex of the addictive personality becomes hypersensitive to the transmitter and will gravitate towards environmental and chemical stimulants.

Ode to rewarding brain stimulation

"After sending a single electric shock to
the axons of dopamine neurons,
extracellular dopamine concentrations
in the dorsal and ventral striatum
rise
within 1.3-10.0 ms
from baselines of 5-10 nM
via intrasynaptic peaks of 500-3000 nM
to extrasynaptic concentrations of 250-500 nM in rats and guinea pigs
and 500-1600 nM in monkeys
(Kawagoe et al. 1992, Dugast et al. 1994, Garris et al. 1994, Cragg et al. 2000)

Concentrations quickly become homogenous
at ~80 nM
within a sphere
of 3.5-4 micrometers in diameter
(Gonon 1997, Cragg & Rice 2004),
which is the average distance
between the dopamine-releasing varicosities
(Doucet et al. 1986).
Maximal diffusion is reached within
75 ms after release onset
and extends to 7-12 micrometers,
even with intact reuptake transport.

Multiple electrical shocks
at intervals of 16.66 to 500 ms (2-60 Hz)
induce peaks
exceeding 4000 nM after 200-300 ms,
which are higher
than those obtained
with the same number
of more widely spaced impulses
(Garris & Wightman 1994, Gonon 1988, 1997)

Owing to the action
of the extrasynaptic dopamine reuptake transporter,
concentrations come back to baseline
within 200 ms
after singel pulses
and within 500-600 ms
after multiple pulses."

- Wolfram Schultz (2007) Multiple Dopamine Functions at Different Time Courses

Dopaminergics

This is the second update to the programming section on the iPlant website and on Knol. 'Dopaminergics' is a play on words like neuroinformatics, but the general idea is something I take very seriously. I think a quantitative understanding of dopamine signalling in the brain will allow us to bridge the gap between sensory input and motor output.

In recent years it has become possible to assign exact numerical values to the dopamine release that accompanies specific rewards and states of attention. Microdialysis probes and other biosensors associate rewards, particularly unexpected rewards and rewarding brain stimulation, with sharp increases in dopamine concentration in the prefrontal cortex and basal ganglia in many animals. States of high or low attention have similarly been associated with high or low concentrations of dopamine in the prefrontal cortex. These numerical relations are referred to as dopaminergics.

Dopaminergics describe the relation between dopaminergic events (e.g. a salient object in the environment, the activation of a deep brain stimulation electrode, the discovery of a solution to a problem), dopamine release (e.g. 20nM increase in prefrontal cortex as evidenced by a microdialysis probe) and brain/mental states (e.g. attention, motivation, learning, memory, motor output). It may be helpful to think of dopaminergics as assembly code for the learning brain.


Early references to the dopaminergics of rewarding brain stimulation:

Garris et al (1997) Real-time measurement of electrically evoked extracellular dopamine in the striatum of freely moving rats. Journal of Neurochemistry;

Fiorino et al (1993) Electrical stimulation of reward sites in the ventral tegmental area increases dopamine transmission in the nucleus accumbens of the rat. Behavioral brain research;

Bean & Roth (1991) Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors. Journal of Neuroscience.