Guest Post: Stephen A. Allsop is the first student from HBCU North Carolina Central University (NCCU) to join the MD/PhD program at Harvard University and MIT—by 2018, he expects to receive his degrees from Harvard Medical School and MIT’s department of brain and cognitive sciences. Allsop is a co-author of the peer-reviewed article, “Decoding Neural Circuits that Control Compulsive Sucrose Eating,” published this January in the prestigious journal Cell. He credits NCCU and his mentor there, biology professor Dr. Antonio Baines, for providing the firm foundation on which he is building his research career.
In this post, he provides some insight on optogenetics, a relatively new research approach that is revolutionizing neuroscience.
Mental health disorders remain a growing medical concern worldwide. That’s due, in part, to underdevelopment and under-implementation of effective treatments. The dearth of effective treatments stem from a lack of knowledge concerning the basic mechanisms underlying the development and progression of psychiatric diseases—acquiring that knowledge is a major goal of contemporary neuroscience research.
Neuroscientists face a number of challenges achieving that goal. Among them are the considerable ethical and technological limitations to experimenting on humans. For example, invasive techniques that would be inappropriate to use on humans are required to establish direct links between detailed brain mechanisms and specific symptoms in psychiatric diseases. Another challenge is that drug development is expensive, and thus, it is cheaper to validate potential drugs using animals prior to human testing.
Nonetheless, some invasive methodologies and novel technologies used on animal models have yielded new and potentially broadly useful information about the basic mechanisms involved in psychiatric behaviors. One such novel technology—optogenetics— has provided us with many new insights about the possible way brain circuitry affects behaviors seen in psychiatric disorders.
As the name suggests, optogenetics involves the use of light. Specifically, light-sensitive proteins called opsins are expressed in neurons and then activated by light, causing the neurons to be depolarized or hyperpolarized. (See image below.) Using various activating techniques, researchers can turn on, or block, specific neural circuits at defined times—on the timescale of milliseconds. Not only do these techniques allow for strict temporal control but they also allow neuroscientists to define the specific circuits, populations, or regions in the brain they wish to control. That level of control has revolutionized neuroscience.
Many labs across the world have used optogenetics to explain the function of various neuronal circuits. Dr. Kay Tye’s lab at MIT, to which I belong, is emerging as a leader in the field. Our lab combines novel and traditional neuroscience techniques to unravel the mysteries of the role brain circuits play in behaviors relevant to psychopathologies.
One recent study from the Tye lab—published earlier this year in the journal Cell—sheds light on how reward-processing and feeding circuits in the brain might contribute to eating disorders. My colleagues and I studied the connection between the lateral hypothalamus (LH) and the Ventral Tegmental Area (VTA). The LH is an area in the brain known to be important for many functions such as eating, sex, and social behavior; the VTA is an area known to be important for reward-processing and addiction. This study, led by our principal investigator Dr. Tye and graduate student Edward Nieh, generated a lot of interest and was covered by many popular news outlets, including USA Today, Forbes, Science News, The Scientist, Science Daily, Medical Daily, and MIT News.
To demonstrate the role of the LH-VTA circuit, we placed mice in an arena where they had to cross a grid that delivered mild shocks in order to get a sugar reward. When the LH-VTA circuit was optically stimulated, mice were willing to endure higher shocks in order to get the reward. Inhibiting the circuit, however, made mice less willing to endure shocks.
We also showed that the LH-VTA circuit is important for compulsive eating: Stimulating the LH-VTA circuit caused mice that were already full to continue eating. (See video above.) Surprisingly, though, mice that were hungry chose to eat even when the circuit was inhibited. These results are fascinating because they imply that inhibiting this circuit can curb compulsive eating while leaving normal feeding behaviors intact. Thus, the LH-VTA circuit may be important as a target of potential therapeutic strategies for eating disorders.