A team of investigators from the Massachusetts General Hospital (MGH) Center for Regenerative Medicine has identified a population of brain cells that appear to play a role in calibrating behavioral responses to potentially threatening situations. In their report published in Nature Neurosciencethe researchers describe how activation of a particular group of cells in a deep-seated brain structure, the dorsolateral septum, regulates terrible behavior in mice placed in a context that they have learned to relate to an unpleasant sensation or connection that is similar but not associated with the unpleasant sensation.
"A fundamental question in neuroscience is to understand how the brain conducts behavior," says Amar Sahay, Ph.D., of the MGH Center for Regenerative Medicine, senior author of Nature Neuroscience paper. "The Hippocampus has long been recognized as an important role in coding our environmental context – the details of episodic memories – so it is not surprising that the way in which this context is coded dictates how we respond to subsequent experiences. If we go down an alley – whether we go slow or fast, or if we avoid it altogether – may depend on whether this spawn was associated with an unpleasant experience or similar to the one. This information in the environment is calculated in the hippocampus and relayed to subcortical regions such as the amygdala, the hypothalamus and the nucleus accumbens, which ultimately mediate our behavioral reactions. "
In order to identify neural pathways that relate contextual information on potential threats from the hippocampus to sub-cardiac circuits, the author Antoine Besnard, Ph.D., a postdoctoral researcher in Sahay's laboratory, examined a former model of these pathways by mapping the entire brain regions activated during a task where mice learn to discriminate between a context, such as a box of dark colored walls, where they experience a mild footstool and a similar context without the unpleasant stimulus.
The investigators were surprised to find that a potential hippocampal circuit and one of its outputs – a subcortical region called dorsolateral septal (DLS) – provoked the most sensitive of the two relationships. DLS is made of inhibitory neurons that suppress the activity of other neurons; and investigators found that a large population of DLS neurons express regulatory hormone somatostatin and directly receive hippocampal signals.
Use of a miniature single-photon microscope implanted over DLS in mice in which somatostatin-expressing cells had been genetically labeled showed that a subpopulation of somatostatin expression of DLS cells was less active as the mice froze the movement after being placed in the foot-neck. associated with context, but was more active when the animals began to move or if they were placed in a neutral context that was not associated with discomfort. The team found that tracking the physiological activity of this somatostatin-expressing DLS subpopulation could predict how the animal would behave when placed in the foot-neck associated context, but not in a neutral context. Artificial optogenic stimulation of these cells induced mice to move in the foot-neck associated context, and their inhibition induced the animals to freeze.
"Our results suggest that a potentially linked subpopulation of somatostatin-expressing cells in the DLS acts as" threat sensors "that directly relay complex calculations from the hippocampus to modulate aspects of defensive behavior – such as arrest or motion – and thus calibrate motion. basic reading of higher brain calculations, "says Sahay, Associate Professor of Psychiatry at Harvard Medical School. "These threat sensors may be targets for correcting pathological responses to what may be perceived as environmental threats – as in over-generalization of fear in post-traumatic stress disorder. Other subpopulations of these somatostatin-expressing DLS cells may relate inputs from various hippocampal and cortical regions. to discrete subcortical goals to convey a wide range of behavioral reactions, something we are actively investigating. "
Investigators identify neural circuits, genetic & # 39; switch & # 39; that maintain memory clarity
Antoine Besnard et al. Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses Nature Neuroscience (2019). DOI: 10.1038 / s41593-018-0330-y
Massachusetts General Hospital
Study identifies brain cells that modulate behavioral response to threats (2019, February 11)
February 11, 2019
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