Donald Doherty's blog

Author: Donald Doherty

  • Flipping the On-Off Switch for Eating

    This week an article was published that shows when a specific set of brain cells is activated, the animal eats whether they’re already fed or not (see the video above; “The Inhibitory Circuit Architecture of the Lateral Hypothalamus Orchestrates Feeding” published September 27, 2013 in Science). The target location of these neurons, the hypothalamus, has been known to be important in the control of eating behaviors but the precise brain circuitry driving the three “F”s – fighting, feeding and sex – has not been shown. The new research describes what looks to be a key piece of brain circuitry involved in eating behaviors.

    The scientists genetically manipulated neurons in a structure known as the bed nucleus of the stria terminalis so that, when light was shined on them through fiber optics, they became electrically active and released their inhibitory chemicals (neurotransmitters) onto target neurons in the lateral hypothalamus. This decreased (inhibited) the activity of excitatory neurons in the lateral hypothalamus that contained a specific protein known as the vesicular glutamate transporter-2 protein. The result was a dramatic increase in feeding behavior.

    In other words, excitatory neurons in the lateral hypothalamus seem to suppress feeding behavior. Decrease the activity of those neurons and feeding behavior is turned on. They appear to act as an on-off switch for eating. The potential therapeutic importance of these neurons is clear, especially in the United States with the highest rate of obesity in the world. However, recent public exposure of processed food industry practices presents troubling ethical dilemmas.

    Last week I attended a lecture by the journalist Michael Moss where he talked about his new book “Salt Sugar Fat: How the Food Giants Hooked Us.” Moss states that much of the problem with obesity in the United States is due to the abundance of cheap, calorie-rich, processed food. He goes further and presents evidence that the companies producing processed foods use scientific research data to design the food they market to be maximally attractive to consumers. Makes sense. A company wants to sell product. Best if it sells a lot of product over and over again. The dilemma arrises when we contemplate when a line is crossed from making extraordinarily attractive food to creating additive substances.

    It would be interesting to feed the mouse in the video above sugary cereal to see if this same “switch” was turned on. The research team may have begun describing part of the very circuit activated when a person experiences pleasure, termed bliss in the industry, that companies target when developing a product. It’s interesting that funding for the study included drug and alcohol abuse agencies. This is a complex, fascinating, and very important topic. I highly recommend reading “Salt Sugar Fat: How the Food Giants Hooked Us.”

  • A Human Brain Atlas on the Internet

    BigBrain is a high resolution three dimensional atlas of the human brain.

    Anatomy is the foundation of brain science. Understanding where something happens in the brain often tells us a lot about what happened. Rhythmically active neurons in the brainstem help drive breathing. Neurons in the cortex that respond to sight help us to see. Those that respond to sound help us to hear. Place matters in the brain.

    The Allen Brain Atlas has been a pioneer in providing digital mouse brain atlases where scientists may associate data with locations in the brain. A recent article (“BigBrain: An Ultrahigh-Resolution 3D Human Brain Model” published June 21, 2013 in Science) announced a new “free” and “publicly available” human brain atlas named BigBrain.

    The BigBrain atlas shows brain tissue at a resolution of 20 micrometers. In contrast, the Allen Brain Atlas displays mouse brain tissue at a resolution of 1 micrometer. Storing a digital record of the human brain recorded at the 1 micrometer resolution would take up about twenty-one thousand terabytes of memory, which would exhaust current computing capabilities for interactive exploration. The brain of a 65 year old female was recorded and saved at the 20 micrometer resolution, which resulted in about one terabyte of data.

    You can see from the video above that BigBrain appears to be a stunning human brain atlas. I’ve applied for access to BigBrain but haven’t received confirmation or denial yet so I haven’t been able to experience the atlas first hand. Unfortunately, unlike the Allen Brain Atlas, BigBrain is only available if the system administrators at McGill University provide you access.

  • Manipulating Memories in the Brain

    The first thing that comes to my mind when I hear people talk of memories is that they are speaking about something that presents itself as an image to their mind. An image retrieved from the recent to distant past. The image may be of me at about five years of age sitting on the California desert sand watching black ants busily running in and out of an entrance surrounded by a pile of sand miraculously extracted from the ground to make way for their tunnels. Introspection and research makes clear, however, that many types of memories exist including many that are not presented as images to the mind.

    Figure 1. Labeled dentate gyrus neurons are the active neurons during learning and memory formation. Precisely which neurons are active depends on what is being remembered. The top left photo shows active neurons labeled red and then later an active set labeled green to the same learning and memory context. In the magnified view at top right you can see that many neurons are labeled with both red and green (yellow) indicating that the same neurons were activated each time. At lower left active neurons labeled red were presented with a different learning and memory context than those labeled green. In the magnified view at lower right a preponderance of neurons show distinct red or green labeling indicating that distinct sets of neurons were activated by the different learning and memory contexts. From figure 2 in “Creating a False Memory in the Hippocampus” published July 26, 2013 in Science.

    A remarkable study reported this summer in the research article “Creating a False Memory in the Hippocampus” (published July 26, 2013 in Science) received a lot of attention in the popular press. The study deserves our attention because of the elegant experimental techniques the research team developed to help observe and understand memory formation and its effects on behavior.

    The type of memory the research team created in mice is known as contextual memory. It’s like memory that makes you feel uneasy when you walk to that corner of the garage where some years ago you stepped on a nail that punctured your foot. You formed a contextual memory with the result that you avoid that particular corner of the garage.

    Some mice in this study formed contextual memories associated with active neurons labeled red in a part of the brain known as the dentate gyrus. The same contextual memories were activated in the same set of mice at a later point in time but this time the active neurons were labeled green. Mostly the same neurons were labeled with both red and green (emitting yellow) which indicated that the same contextual memory activated the same set of neurons at different points in time (see Figure 1 above). When mice formed different contextual memories, different sets of neurons were active.

    Now here is the how they do the false memory trick. Using fiber optic cables, the scientist can activate just the red subset of neurons using red light or the green subset of neurons using green light. Imagine if the neurons that were active in your brain when you stepped on that nail were labeled in red and then, at some later date, reactivated using red light. That’s what was done in this study. While the mouse was exposed to events that resulted in contextual memory associated with the green labeled neurons, the research team used red light to activate the red labeled neurons. It’s as if you felt uneasy and avoided the sunflower growing in the front yard because, while you stood next to the sunflower, the neurons in your head associated with stepping on the nail in the garage were activated using red light.

    These are powerful techniques developed to help us understand the brain. However, notice that we remain a long way from understanding how exactly an active set of neurons results in us feeling uneasy. How it is that this uneasiness is brought to mind? Many have speculated but the step from correlation to experience remains a mystery.