Unlocking the Brain’s Fear Circuitry: A Pathway to Survival Responses

Summary: Scientists have identified a new neural pathway that plays a crucial role in how the brain shifts to high-intensity fear responses. This discovery pinpoints a previously unknown connection between the prefrontal cortex and the amygdala, crucial for emotional regulation and decision-making during fearful situations.

The findings could pave the way for novel treatments for psychiatric conditions like PTSD and anxiety disorders by better understanding these fear response mechanisms. This breakthrough emphasizes the importance of the prefrontal cortex’s role in modulating fear through its influence on the amygdala, offering potential for therapeutic advancements in mental health.

Key Facts:

  1. Researchers have discovered a novel neural pathway that regulates the transition to high-intensity fear behaviors, crucial for survival, through a connection between the prefrontal cortex and the amygdala.
  2. This pathway’s dysregulation can lead to psychiatric illnesses such as PTSD and anxiety disorders, highlighting its significance in understanding and treating these conditions.
  3. The study utilized advanced techniques like in vivo calcium imaging, chemogenetic, and optogenetic manipulation to uncover and influence this pathway in mice, opening new avenues for therapeutic interventions.

Source: Northwestern University

Scientists have discovered a new neural pathway involved in how the brain encodes the transition to high-intensity fear response behaviors that are necessary for survival, according to a recent study published in Nature.

Jones Parker, Ph.D., assistant professor of Neuroscience, of Pharmacology and of Psychiatry and Behavioral Sciences, was a co-author of the study.

In mammals, the amygdala is involved in generating survival responses and transitioning to different high-intensity fear behaviors such as freezing or immobility (avoidance behavior) to escaping (flight behavior) in response to perceived threats.

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As for next steps, Fadok said his lab is currently performing a physiological analysis of the dorsal peduncular region of the prefrontal cortex to better characterize its neuronal population and overall function. Credit: Neuroscience News

When these responses are dysregulated in humans, however, they can cause psychiatric illnesses such as post-traumatic stress disorder or anxiety and panic disorders. Until now, the precise source of the neural circuits involved in these responses had remained poorly understood.

In the current study, the investigators used mouse models developed by the laboratory of Jonathan Fadok, Ph.D., the Burk-Kleinpeter Inc. Professor in Science and Engineering at Tulane University and senior author of the study, to identify the neural circuits involved in the escalation of behavioral responses to high-intensity fearful situations.

Using a combination of techniques developed by Parker’s lab, including in vivo calcium imaging, the scientists discovered a previously unknown connection between the brain’s prefrontal cortex and the amygdala, which are involved in emotional regulation and adaptive decision-making, that controls and regulates this transition to high-intensity fear behaviors.

The scientists then used chemogenetic and optogenetic techniques to manipulate this novel pathway in the mice and discovered a new neuronal projection involving neurotransmitter release from excitatory neurons in dorsal peduncular region of the prefrontal cortex, an understudied area of the brain, to neurons in the amygdala.

“We have the cortex, which is projecting to this ancient brain structure involved in fear processing, that taps into the amygdala and directly scales the level of fear that the animals are experiencing,” Parker said.

Furthermore, molecularly characterizing such regions of the brain involved in this escalation of fear responses may help identify novel therapeutic targets for different psychiatric illnesses, Parker added.

“This links the prefrontal cortex—this area that expanded over evolution in humans, an area involved in expectations and predictions about our environment—to the ancient brain circuit that controls fear, so this could contribute to pathologies involving fear and how we conceptualize them,” Parker said.

As for next steps, Fadok said his lab is currently performing a physiological analysis of the dorsal peduncular region of the prefrontal cortex to better characterize its neuronal population and overall function.

“By understanding what we call top-down control, so cortical control over these ancient structures that regulate fear, I think we can make major inroads to developing better treatments,” Fadok said.

About this neuroscience research news

Author: Marla Paul
Source: Northwestern University
Contact: Marla Paul – Northwestern University
Image: The image is credited to Neuroscience News

Original Research: Closed access.
Top-down control of flight by a non-canonical cortico-amygdala pathway” by Chandrashekhar D. Borkar et al. Nature


Top-down control of flight by a non-canonical cortico-amygdala pathway

Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder.

Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA); however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown.

Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main amygdalar output nucleus mediating conditioned responses to threat.

Using a behavioural paradigm that elicits both conditioned freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary and sufficient for both avoidance behaviour and flight.

Furthermore, we found that DP neurons synapse onto neurons within the medial CeA that project to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.

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