Oxytocin neurons in the paraventricular nucleus of the hypothalamus. Oxytocin neurons were labeled by genetically targeting of a fluorescent reporter. Labeled neurons were visualized with light-sheet fluorescence microscopy and rendered in 3D bilaterally throughout the entirety of the PVH to generate this animation. The video provides a view of oxytocin neurons, shown in different shades of red, in the PVH. They are viewed first from the rostrocaudal (front to back) perspective, then from a dorsal (top-down) view, and then from a lateral view before zooming in.
Researchers from the Vanderbilt University School of Medicine Basic Sciences have uncovered the first example of activity-dependent development of hypothalamic neural circuitry. Although previous research has shown that the hormone leptin acts directly on hunger neurons through leptin receptors to promote the development of neural circuitry, results that will be published in PNAS on Nov. 25 indicate that certain neurons that do not express leptin receptors are nonetheless sensitive to its activity.
The research, led by the lab of Richard Simerly, Louise B. McGavock Professor and professor of molecular physiology and biophysics, also supports a novel role for leptin in specifying the development of neural circuits involved in autonomic regulation and food intake. His lab found that silencing the activity of hunger neurons (called “AgRP” neurons) during the critical, postnatal period of neuronal circuitry development may exert lasting effects on the structure and function of circuits that control energy balance.
Leptin is a hormone that, in adults, regulates hunger by providing a sensation of satiety and helps maintain body weight on a long-term basis. In the weeks following birth, however, leptin also helps direct the formation of circuits that control homeostatic functions.In their PNAS paper, the Simerly lab describes three primary results:
Leptin is required for the normal development of neural connections between hypothalamic oxytocin neurons, which link AgRP neurons with brainstem neurons that coordinate autonomic responses associated with feeding, even though oxytocin neurons in this pathway do not express leptin receptors.
The development of the neural circuits that link the hypothalamus and brainstem are dependent on the activity of leptin-sensing AgRP neurons during a postnatal, critical period of hypothalamic development.
Perturbing of the neural activity in hypothalamic neurons can permanently alter the functional regulation of brainstem regions that coordinate gastrointestinal processes related to feeding.