Overreaction of Brain’s Alarm Clock May Be Involved in PTSD

Robert C. Froemke, PhD, Assistant professor NYU Langone and Skirball Institute of Biomolecular Medicine New York

MedicalResearch.com Interview with:
Robert C. Froemke, PhD, Assistant professor
NYU Langone and Skirball Institute of Biomolecular Medicine
New York

Medical Research: What is the background for this study? What are the main findings?

Dr. Froemke: We studied how a brain area called the ‘locus coeruleus’ is involved in hearing. The locus coeruleus is the brain’s alarm clock, it’s a small region deep in the brainstem that is responsible for arousal and wakefulness, activated by surprising or potentially dangerous events. The locus coeruleus releases the neurochemical noradrenalin (similar to adrenalin) throughout the brain to greatly increase brain activity, and so might convey the significance of sounds related to past events that were very important or startling in some way (like the sound of an alarm, a baby crying, or other sounds that require immediate attention).

We found that sounds related to surprising events can come to directly activate the locus coeruleus, meaning that this brain area can learn from past experience. This learning happens quickly (within seconds to minutes) and can be incredibly long-lasting, up to weeks as measured in our study, and we suspect indefinitely or all life-long. We studied this by training lab rats to respond to sounds, poking their nose in a hole to get a food reward whenever they heard a certain sound. We activated the locus coeruleus briefly in some of these animals, and observed that they were much more sensitive to this sound and learned much faster than other unstimulated animals. We made recordings of electrical activity in the locus coeruleus and the auditory cortex, one of the major ‘hearing’ parts of the brain. In stimulated animals, sounds activated the locus coeruleus within tens of milliseconds, releasing noradrenalin into the auditory cortex to greatly boost the audio processing there- making almost every neuron respond very vigorously to that special sound.

Medical Research: What should clinicians and patients take away from your report?

Dr. Froemke: The locus coeruleus is absolutely essential for brain function, particularly waking up and paying attention to important occurrences in the environment. Hearing- including speech and language skills- require paying attention to certain sounds, ignoring background noise and understanding the meaning of words and phrases, which are learned from experience. We think that the locus coeruleus is part of this system for understanding what different sounds represent.

Some sounds, like predator growls, gunshots, oncoming traffic or the cry of your baby, are very important to learn about in a way that sometimes doesn’t allow much room for error. We think that the locus coeruleus might enable these very important sounds to be quickly learned. However, sometimes it can go too far, and there’s evidence that the locus coeruleus and noradrenalin are involved in PTSD and anxiety disorders, if sounds that are otherwise innocuous come to be associated with hazards.

PTSD is a very serious condition, and although the locus coeruleus and noradrenalin have long thought to be involved in PTSD, beta-blockers (that reduce some of the action of noradrenalin) have had limited utility as a treatment. Our results suggest instead that other aspects of the noradrenalin system (targeted by alpha-blockers) might be involved in the memory formation we studied here. But also that anxiety and fear memories are widely distributed throughout the brain, making them particularly resilient to treatment.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Froemke: We are interested in determining what can reverse or augment memory formation in the locus coeruleus, to understand if or how this process might be related to PTSD. Also, how does sound information get into locus coeruleus, what are the brain connections that send audio information there, and how specific is this for certain types of sounds? Are all of these alert sounds learned from experience, or might there be some innate preference or bias to some kinds of particularly important or dangerous sounds?


Ana Raquel O Martins & Robert C Froemke.
Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex.
Nature Neuroscience, 2015 DOI: 10.1038/nn.4090

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Robert C. Froemke, PhD (2015). Overreaction of Brain’s Alarm Clock May Be Involved in PTSD