On Circadian Rhythms & Physiology

from reference 1

Circadian rhythms govern our state of arousal, informing us when to go to sleep and (for some) pulling us up from the pleasant depths of slumber. Further, because the physiological goals of sleep are so different from wakefulness (learning while awake & consolidating memories while asleep, using muscles to do work during the day & repairing them at night, et cetera), the circadian rhythm is also used to regulate many bodily properties and dynamics. An example of this can be found in a recent paper published in the journal Cell1. The authors of this study found that the degree of electrical coupling between rod cells and cone cells in mice and goldfish is modulated by circadian rhythms.

Rod cells are relatively color-insensitive cells in the eye while cone cells are color-sensitive (with different subtypes having being sensitive to different parts of the spectrum). Thus, for the purposes of accurate perception of the visual world, one wouldn’t normally want to link the activity of rods and cones because this would mix the color-insensitive responses with the color-sensitive ones, effectively washing out color information. However, as the day goes on and it gets dark, the argument goes, color matters less, and the paucity of light leads to the strategy of pooling responses across all light-responsive retinal cells. This is what is achieved by such circadian-rhythm-induced electrical coupling, pooling of responses to illumination.

References:
1. Ribelayga C, Cao Y, Mangel SC. The circadian clock in the retina controls rod-cone coupling. Neuron, 59: 790-801, 2008.

On Martian Snow

As reported in the Washington Post, NASA’s Phoenix Lander (pictured above) has detected snowfall on Mars. Using LASER based scanning technology, the remote probe was able to spot flakes in the atmosphere and track their descent for more than a mile. However, Phoenix was not able to discern whether the snow actually landed on the surface of the planet. The idea, however, of snow-fall on Mars is a romantic and beautiful one, it just blossoms in my imagination.

On Tree Drinking

from reference 1

Plants don’t have hearts to pump fluids throughout their systems, so how do they generate the pressure to move water against the force of gravity from their roots to their shoots (leaves)? Capillary action (the tendency of a fluid to move through small spaces due to it’s molecular constituents cohesive properties or surface tension) can explain the movement of water over small distances, but it cannot account for the large scale movement of water from the bases to the tips of tall trees like the Giant Sequoia of Redwood Forest.

Instead, it has long been thought that evaporation of water at the leaves draws water up in a long continuous column from the root, a process known as transpiration. This hypothesis was recently verified in the form of an artificial model1. Abraham Stroock and his graduate student at Cornell University built a small (10 cm) proof-of-concept tree model with artificial membranes representing roots and leaves and small “microfluidic” channels connecting them. Though small, this device demonstrates the functional capacity of the evaporation/water-column idea, and might eventually be used to test failures of this model (such as when air-bubbles intervene in the column) and to draw small amounts of water out of hard to reach places.

References:
1. Wheeler TD, Stroock AD. The transpiration of water at negative pressures in a synthetic tree. Nature, 455(7210): 208-212, 2008.

On Subconscious Action

from reference 1

The subconscious components of our minds are more powerful than many admit, or feel comfortable admitting. As we go about our lives, our subconsciousness learns about aspects of our existence that might otherwise clutter our thoughts with a distracting chatter of activity: what pressure must I apply to the coffee cup in order for it to remain in my grasp, what route must I take through the throng of commuters in Penn-station to avoid colliding with others, has my blood-sugar dropped below the threshold where I experience hunger, et cetera. In fact, to some extent, the subconscious mind has access to information that the conscious mind does not, as in the muscle tension and blood-sugar examples. Understanding how these abilities are segregated between conscious and unconscious, and to what extent that question even makes sense to ask at both a behavioral and neurophysiological level are of fundamental interest to the understanding of consciousness and human neurological function in general.

A recent study speaks to this topic by probing the extent to which the subconscious can learn about the association between briefly presented visual cues and a monetary reward1. Specifically, Chris Frith & colleagues had subjects play a game where the ability to win money in a given turn of the game was predicted by a visual cue which was presented too briefly to be consciously perceived (see instructions below2). The results of this study suggest that humans are reliably able to subconsciously learn the rewarding value of these visual cues. Importantly, in a control experiment, the researchers demonstrated that the subjects were unable to discriminate between the stimuli without the monetary reward/punishment scheme.

Given the abilities of humans (sketched above) to relegate processing to the subconscious, this finding isn’t that surprising. However, this paper demonstrates the importance of feedback (reward or punishment) for instructing the subconscious. Furthermore, the fact that something as arbitrary as the conscious perception of promised financial reward can serve as the feed-back signal suggests a fundamental role for this type of learning that isn’t limited to certain acts, but might underlie the learning abilities of humans in general.

References/Notes:
1. Pessiglione M, Petrovic P, Daunizeau J, Palminteri S, Dolan RJ, Frith CD. Subliminal instrumental conditioning demonstrated in the human brain. Neuron, 59(4): 561-567, 2008.

2. “The aim of the game is to win money, by guessing the outcome of a button press.

At the beginning of each trial you must orient your gaze towards the central cross and pay attention to the
masked cue. You will not be able to perceive the cue which is hidden behind the mask.

When the interrogation dot appears you have 3 seconds to make your choice between
– holding the button down
– leaving the button up
If you change your mind you can still release or press the button until the 3 seconds have elapsed.

‘GO!’ will be written in yellow if, at the end of the 3 seconds delay, the button is being pressed.

Then we will display the outcome of your choice. Not pressing the button is safe: you will always get a
neutral outcome (£0). Pressing the button is of interest but risky: you can equally win £1, get nil (£0) or
lose £1. This depends on which cue was hidden behind the mask.

There is no logical rule to find in this game. If you never press the button, or if you press it every trial,
your overall payoff will be nil. To win money you must guess if the ongoing trial is a winning or a losing
trial. Your choices should be improved trial after trial by your unconscious emotional reactions. Just
follow your gut feelings and you will win, and avoid losing, a lot of pounds! “

On The Genetic Basis of Schizophrenia

“… what a narrow ridge of normality we all inhabit, with the abysses of mania and depression yawning to either side.”1

from reference 2

Schizophrenia is a debilitating condition, chronic in nature, that affects approximately 1 in a hundred people worldwide. Although able to strongly suggest a genetic basis, past research has not been truly successful in determining the hereditary underpinnings of this combined neurological and psychiatric disorder.

from reference 3

Two papers, published in the journal Nature, have pushed this field of research farther than ever before, establishing schizophrenia-relevant chromosomal loci and using larger numbers of patients than in the past, for stronger statistical power2,3. These studies focused on two types of chromosomal abnormalities, single nucleotide polymorphisms (SNPs; changes to single bases) and copy-number variations (CNVs; changes in the number of copies of one or more whole genes). Both studies confirmed previous findings of a CNV locus associated with schizophrenia, and validated each other’s implication of two new CNV loci. Although it is still unclear how such information might be used, this is a cause for enthusiasm regarding the treatment of schizophrenia, and the possibility of determining genetic basis for other psychiatric disorders.

References:
1. Sacks, O. A Summer of Madness. The New York Review of Books, LV(14): 57-61, 2008.

2. Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Möller HJ, Hartmann A, Shianna KV, Ge D, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di Forti M, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Mühleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nöthen MM, Peltonen L, Collier DA, St Clair D, Stefansson K, Kahn RS, Linszen DH, van Os J, Wiersma D, Bruggeman R, Cahn W, de Haan L, Krabbendam L, Myin-Germeys I; Genetic Risk and Outcome in Psychosis (GROUP). Large recurrent microdeletions associated with schizophrenia. Nature, 455(7210):232-236, 2008.

3. Stone JL, O’Donovan MC, Gurling H, Kirov GK, Blackwood DH, Corvin A, Craddock NJ, Gill M, Hultman CM, Lichtenstein P, McQuillin A, Pato CN, Ruderfer DM, Owen MJ, St Clair D, Sullivan PF, Sklar P, Purcell SM, Stone JL, Ruderfer DM, Korn J, Kirov GK, Macgregor S, McQuillin A, Morris DW, O’Dushlaine CT, Daly MJ, Visscher PM, Holmans PA, O’Donovan MC, Sullivan PF, Sklar P, Purcell SM, Gurling H, Corvin A, Blackwood DH, Craddock NJ, Gill M, Hultman CM, Kirov GK, Lichtenstein P, McQuillin A, O’Donovan MC, Owen MJ, Pato CN, Purcell SM, Scolnick EM, St Clair D, Stone JL, Sullivan PF, Sklar P, O’Donovan MC, Kirov GK, Craddock NJ, Holmans PA, Williams NM, Georgieva L, Nikolov I, Norton N, Williams H, Toncheva D, Milanova V, Owen MJ, Hultman CM, Lichtenstein P, Thelander EF, Sullivan P, Morris DW, O’Dushlaine CT, Kenny E, Waddington JL, Gill M, Corvin A, McQuillin A, Choudhury K, Datta S, Pimm J, Thirumalai S, Puri V, Krasucki R, Lawrence J, Quested D, Bass N, Curtis D, Gurling H, Crombie C, Fraser G, Kwan SL, Walker N, St Clair D, Blackwood DH, Muir WJ, McGhee KA, Pickard B, Malloy P, Maclean AW, Van Beck M, Visscher PM, Macgregor S, Pato MT, Medeiros H, Middleton F, Carvalho C, Morley C, Fanous A, Conti D, Knowles JA, Ferreira CP, Macedo A, Azevedo MH, Pato CN, Stone JL, Ruderfer DM, Korn J, McCarroll SA, Daly M, Purcell SM, Sklar P, Purcell SM, Stone JL, Chambert K, Ruderfer DM, Korn J, McCarroll SA, Gates C, Daly MJ, Scolnick EM, Sklar P. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature, 455(7210):237-241, 2008

On the nth Sense

from reference 1

It is widely documented that pheromones effect the behavior of insects, fish and mammals. However, locating both the pheromone molecules themselves and the anatomy for detecting them has proven challenging. A recent study, however, has identified the cells responsible for detecting so-called ‘alarm pheromones’ in mice1.

The image above shows the implicated structures at various levels of detail. In the upper left, you can see a section of a mouse head, with a box around the GG: the Gruenberg ganglion, named for Hans Gruenberg, who first identified the set of cells in 1973.

There is every reason to assume that human beings are susceptible to the effects of pheromones, especially since the ganglion identified in the study mentioned above is present in humans. The prospect of having our behavior (or physiology in general) manipulated by artificial use of these molecules is both exciting and scary.

References:

1. Brechbühl J, Klaey M, Broillet M-C. Grueneberg ganglion cells mediate alarm pheromone detection in mice. Science 321: 1092-1095, 2008.

On Memory and Experience

from reference 1

As reported in the New York Times, a new study has demonstrated an aspect of memory that has long been hypothesized. That being: the same neurons that fire during an experience fire during the memory of that experience. The research, published in the journal Science, relies on recordings from the brains of epileptic patients undergoing surgery to remove the parts of their brain which cause excesses of neuronal activity, essentially the only way to record the activity of neurons in awake human beings1.

The authors of the study took an approach where they recorded the activity of single hippocampal brain cells while subjects were watching a variety of video clips. Unsurprisingly, certain cells responded best to certain clips. Then, after a brief interim during which the experimenters distracted the patients, they asked the subjects to recall the video clips. Not only did the activity of the neurons during recollection correlate with activity during first viewing, the experimenters were able to predict which video clip the subjects were remembering based on the recorded activity! Interestingly, however, the hippocampus (the area of the brain being recorded from in this study) is not required for the recall of long term memories. Thus, in some ways this work further deepens the mystery of how short term versus long term memories are encoded in the brain and the involvement of hippocampus in these processes; a subject previously touched on in this forum.

Reading about this research reminded me of my favorite definition of memory, as the ability to:

“repeat a mental or physical act after some time despite a changing context…. We stress repetition after some time in this definition because it is the ability to re-create an act separated by a certain duration from the original signal set that is characteristic of memory. And in mentioning a changing context, we pay heed to a key property of memory in the brain: that it is, in some sense, a form of constructive recategorization during ongoing experience, rather than a precise replication of a previous sequence of events.

…the key conclusion is that whatever its form, memory itself is a [property of a system]. It cannot be equated exclusively with circuitry, with synaptic changes, with biochemistry, with value constraints, or with behavioral dynamics. Instead, it is the dynamic result of the interactions of all these factors acting together, serving to select an output that repeats a performance or an act.

The overall characteristics of a particular performance may be similar to previous performance, but the ensembles of neurons underlying any two similar performances at different times can be and usually are different. This property ensures that one can repeat the same act, despite remarkable changes in background and context, with ongoing experience.”2

References:

1. Gelbard-Sagiv H, Mukamel R, Harel M, Malach R, Fried I (2008) Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall. Science 10.1126/science.1164685
2. Edelman GM, Tononi G (2000) A Universe of Consciousness: How Matter Becomes Imagination, Basic Books, New York

On the Importance of Single Spikes

from reference 1

As mentioned numerous times before in this forum, neurons in the brain communicate by action potentials: pulses of voltage that usually propagate from the cell body (soma) down a specialized outcropping of membrane called the axon which synapses onto other neurons. Usually, these synapses link pre-synaptic axons to post-synaptic dendrites, cellular structures specialized for recieving input.

Until recently, it was thought impossible for a single action potential, initiated in soma, to cause a second, post-synaptic neuron to fire an action potential; rather, as has been extensively documented, single neurons require many simultaneous dendritic inputs which are summed together to cause an action potential to be initiated in the soma. Recent research, however, has identified a cell type found exclusively in the cerebral cortex of human beings which seems to contradict this generalization. These neurons, termed “chandelier cells” are able to cause a chain of post-synaptic events (action potentials in several cells) lasting up to, on average, 37 milliseconds, ten times longer than had been previously assumed possible1.

The article reporting these findings, published in the estimable journal PLoS Biology, describes one feature that the authors feel is of paramount importance to this phenomenon. Apparently chandelier cells are much more likely to make axo-axonic connections. That is, they send their pulses of activity not to dentrites, but to other axons. The reason for this somewhat exotic type of connectivity is that chandelier cells normally turn off the output of other neurons by sending inhibitory signals that cancel action potentials being sent down axons of the chandelier’s targets. It seems then, that single chandelier cell action potentials inhibit other cells which are themselves inhibitory, indirectly exciting the targets of these secondary inhibitory cells.

The relevance of these findings to human cognition or consciousness is unclear, but this represents a significant advancement for our understanding of the functional connectivity of the human brain.

References:
1. Molnár G, Oláh S, Komlósi G, Füle M, Szabadics J, et al. (2008) Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex. PLoS Biol 6(9): e222 doi:10.1371/journal.pbio.0060222

On Behavioral Genetics (II)


from reference 1

Once again, an example of a gene that plays some role in determining a human behavior has been found. Vasopressin, a neuropeptide, has long been known to regulate monogamous behavior in male voles. As with all signalling molecules in the brain, the effects of vasopressin can be changed by variations in its receptors (the molecules that recognize the signal; the lock to the key). Interestingly, recent research indicates that vasopressin plays a similar regulatory role in humans. Specifically, research published in PNAS aimed to determine if there was variability in the pair-bonding behavior amongst men possessing variable copies (none, one or two) of a version of a gene that codes for one subtype of the vasopressin receptor. As can be read from the table above, the work reports that men with more copies of this gene were less likely to be married, and more likely to answer yes to the question: “Have you experienced marital crisis or threat of divorce within the last year?”

References:
1. Walum, H, Westberg, L, Henningsson, S, Neiderhiser, JM, Reiss, D, Igl, W, Ganiban, JM, Spotts, EL, Pedersen, NL, Eriksson, E, & Lichtenstein, P. (2008) Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. PNAS doi: 10.1073/pnas.0803081105