Thinking Fast and Slow about Thirst

Out of all motivational states, thirst should have been a simple one to understand. One feels thirsty when one is dehydrated, which can be detected from blood volume and osmolarity. Drinking water hydrates one’s body and quenches thirst. This is a homeostatic model. Intuitive, right? Well, the strange thing about thirst is that it is quenched within seconds to minutes after drinking water, which is too fast for any changes in the blood to happen. This is as if the brain gets hydrated before the body, which makes little sense since there is no specialized canal that passes water from mouth to brain (thank goodness). On the other hand, the buildup of the thirst drive is usually rather slow, meaning that thirst state can change on both a fast and slow time scale. How does it work?



The touch of a fly

Our sense of touch has an innate connection with our emotions. Gentle touches are soothing for not only us but also other animals. For example, classic experiments by psychologist Harry Harlow in the 1950s found that an infant monkey raised with two robots, one providing food and the other wearing soft cloth, spends more time cuddling with the cloth robot1. When scared, the infant monkey also goes to the cloth robot for protection. Clearly, there is a special pathway that guides touch sensation to the depths of animal instincts. Working out this pathway requires knowledge about the neural circuitry processing touch sensation.


[Throwback Thursday] A hole in sight

Patients with a damaged retina or visual cortex often report hole(s) in their sight. However inconvenient they may seem, these holes in many cases do not bother the patients and are sometimes not noticed at all. How do they block these holes from their awareness? In fact, this is a question that we should all ask ourselves, because we all have natural blind spots in our visual perception. This blind spot is caused by a small region in the back of our eyes that contains no retinal neurons. Instead, this region is dedicated for the retinal output neurons to send signals to the brain. Therefore, we walk around with two holes (one on each side) in our visual field. How do we not notice them, even when we try seeing with only one eye at a time?

8 blind spot

Figure 1. A stimulation to reveal the natural blind spot. After placing the gray patch in their blind spot, Ramachandran and Gregory’s subjects could fill-in the patch with letter strings, even though they could not actually read the filled-in letters.


What does cocaine do in the brain?

Not all drugs can completely change who we are. Cocaine is one of the few with this power. Like many other psychoactive drugs, cocaine was first used as an anesthetic, but its potential effect on one’s mind and will was soon discovered and overshadowed its original usage. Cocaine’s power does not lie within the molecule itself, but rather in its interaction with the brain’s reward system (see a previous TBT post for the discovery of this system).


[Throwback Thursday] A gene to unite hot and hot

It is no linguistic coincidence that high temperature and spiciness share the same word in the English dictionary: they induce the same burning sensation. The biological basis for this commonality was discovered in 1997 by David Julius’s group at UCSF1.


Tagging a snapshot of life with prions

“As you know, in most areas of science, there are long periods of beginning before we really make progress.” – Eric Kandel

In a typical maze experiment, a hungry rat enters a moderately complicated maze, in which it does its best to find a “reward room” with food. After some guesses, the rat finds its way, consumes the food, and is returned to the entrance of the maze. From then on, the rat makes fewer bad guesses and finds the food faster after each round. Eventually, it completely masters the maze layout and finds the perfect route every time. To explain this improvement, scientists have coined the term reward reinforcement, which essentially suggests that the reward that the rat collects at the end reinforces its correct choices, until it eventually learns a perfect route. This model may sound very simple, but is it?


[Throwback Thursdays] The rat that became addicted to shocking its brain

All addictive substances exert their effects by harnessing the powerful reward system that is normally used to guide an animal’s behavior. One simplistic way to build a reward system is to have neurons that carry positive and negative values. These reward centers would then, and have been shown to, be the primary target of the addictive substances. To find these reward centers, researchers must devise a way to stimulate a brain region and ask the animal how it likes it. How can one do this?


3 rat self stimulating

Figure 1. A rat presses the lever to stimulate its own brain. Adapted from Olds 19581.


Toward a Molecular Lego Kit for Engineering Specialized Channels

“What I cannot create, I do not understand.” — Richard Feynman (1988)

An organism’s ability to sense the world ultimately relies on specialized proteins in its sensory neurons to probe the external world on behalf of the entire organism. Channels, a group of proteins that act as gatekeepers of ions, are often delegated to the front end of the job. As a result, highly specialized channels, such as those that sense odors, temperature, and even touch, have evolved in all corners of the world. Over the years, the genetic identities of many such channels have been demystified. Our current challenge lies in pinpointing the nanoscopic means by which they sense the world. To achieving this goal, an inevitable path is to locate the intramolecular modules (often referred to as domains) that grant channels their special ability to sense the environment. Several remarkable studies in recent years have made significant progress in attacking this problem.


The first complete structure of a channel, the bacterial potassium channel KcsA, obtained by Rod MacKinnon’s group in 19981. This work pioneered a new wave of channel structure-function analyses.


Seeing Ghosts with c-fos-derived Tools

“Progress in science depends on new techniques, new discoveries and new ideas, probably in that order.” — Sydney Brenner

Bread, beer, and the flu are only a few of the many ways microbes welcome us to their worlds. By looking into the microbial realms, modern biology has found the genome-engineering tools to put the right transgenes in the right cells. These tools have changed the way researchers study neural circuits. Nowadays, to study the neurons responsible for specific behaviors, researchers typically screen through a library of pre-engineered animals, each expressing transgenes in a distinct group of neurons, with the hope that one of these neuronal populations controls the behavior of interest. Together with other tools, this library approach accelerated the discoveries of specific neurons controlling feeding, drinking, fighting, and parental behaviors. However, despite great effort, this strategy is still limited by the transgenic lines available and helpless when the relevant neuronal populations do not share a common genetic locus. For example, what if one wishes to study how higher-order, olfactory-processing neurons respond to the smell of apple pie? How can we control these pie-smelling neurons if we don’t know who they are?

In picture: an invisible ghost in front of a green screen. Date unknown.