L8 based on Giulia's notes Flashcards
Peripheral stress response - 3 key stress components + how they occur in the body
Psychological responses to stress involve changes in emotion, cognition, arousal, and motivation, which are processed by the brain’s limbic system, cerebral cortex, and modulatory systems. These psychological responses play a critical role in interpreting and reacting to stressors.
Physiological stress responses, on the other hand, are driven by changes in energy metabolism, immunity, cardiovascular activity, reproduction, and digestion. These are regulated by the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, which coordinate the body’s internal state in response to external challenges.
Behavioral stress responses are outwardly visible actions, such as attack, escape, freezing, facial expressions, and reflexes, which are mediated by the somatic nervous system. Together, these components illustrate the complex and integrated nature of the stress response, linking mental, physical, and behavioral processes to prepare the individual to cope with or adapt to stress.
Central stress-regulatory network - its role is
Central stress-regulatory network=involves the processes by which the body detects, regulates, and terminates responses to stress.
What is the difference between afferent and efferent systems?
Afferent systems - stress signal detection
Efferent systems - stress response generation
Describe the regulatory and modulatory systems stress regulation from page 1 of Giulia’s summary
literally go to page 1
How does physiological stress gets detected?
Physiological:
Reactive, largely reflexive responses
Detection of such stressors occurs via specialized sensory systems called interoceptors, which include:
Baroreceptors: Detect changes in blood pressure.
Chemoreceptors: Monitor levels of oxygen, carbon dioxide, and pH in the blood.
Osmoreceptors: Detect changes in fluid balance or osmolarity.
How does psychological stress gets detected?
The amygdala processes and integrates sensory input to evaluate threats and coordinate appropriate defensive or adaptive responses. It acts as a critical hub in both detecting threats and initiating responses to maintain survival.
Amygdala’s activity is regulated and calmed down by prefrontal cortex
What happens neurobiologically when blood pressure drops?
When there is a blood pressure change (bp goes down), such change is detected by the baroreceptors in the carotid arteries and aorta. These sensors send signals to medulla oblongata, which can stimulate sympathetic action and release of NE and inhibit ACH release and parasympathetic action.
This leads to vasoconstriction, increased force of cardiac contraction and increased heart rate
Key Functions of the Amygdala in Threat Appraisal
- Threat Detection and Sensory Processing:
The lateral amygdala (LA) receives sensory input from the environment. This input allows the amygdala to assess the salience (importance) and valence (positive or negative nature) of the threat. - Defensive Reactions and Actions:
The basal amygdala (BA) and central nucleus of the amygdala (CeA) coordinate different types of defensive behaviors:
Defensive reactions: Involve immediate, automatic responses such as freezing or fight behaviors.
Defensive actions: Include more deliberate behaviors like escape or avoidance. - Output to Regulatory Systems:
The central nucleus (CeA), as the primary output region, sends signals to key regions:
Hypothalamus: Activates the HPA axis and the SAM system for physiological responses (e.g., cortisol release, sympathetic activation).
Brainstem: Triggers freezing or fight-or-flight behaviors. - Reward and Motivation Systems:
The nucleus accumbens (NAcc) and related structures are engaged, connecting threat processing with reward and action. This ensures adaptive responses are reinforced.
Bottom-up regulation
Bottom-up regulation begins with stress signals generated by homeostatic imbalances, pain, or inflammation, which are detected and transmitted as ascending information from sensory systems to intermediate processing centers like the brainstem and hypothalamus. These signals provide ongoing feedback about the body’s internal state, influencing “middle management” regions, such as BST and hypothalamus, which integrate this information to coordinate appropriate responses.
Specific Circuits for Threat Processing
Processing Clear and Immediate Threats:
In the presence of a well-defined, immediate threat, sensory input flows directly to the lateral amygdala, followed by the basal and central nuclei, which drive freezing, fight, or escape behaviors. This circuit provides a fast and effective response.
Processing Uncertain or Ambiguous Threats:
When a threat is unclear or ambiguous, additional regions like the bed nucleus of the stria terminalis (BNST) (the extended amygdala) and the hippocampus become involved. These areas help process contextual information to modulate responses and reduce unnecessary actions.
Top-down regulation
Top-down regulation involves descending inputs from higher brain regions, such as the limbic system and prefrontal cortex, which influence how stress is interpreted and managed. These corticolimbic inputs modulate the activity of intermediate integration centers, allowing cognitive and emotional factors, such as experiential learning and innate programs, to shape the stress response. These combined inputs regulate output systems, such as the HPA axis and the sympathetic-adrenal-medullary (SAM) system, which mediate the body’s physiological response to stress.
Which part of amygdala handle stress and how exactly
- Medial Amygdala (MeA):
Plays a supportive role in stress responses but is less emphasized here. - Basolateral Amygdala (BLA):
Acts as the “gateway” for processing external sensory and cognitive inputs related to stress.
It primarily activates in response to psychological stressors, such as social threats or restraint.
It promotes anticipatory responses, preparing the body for expected challenges. - Central Amygdala (CeA):
Acts as the “output hub” of the amygdala.
It primarily responds to physical stressors, like low oxygen levels or immune challenges.
It drives reactive responses, which are immediate and automatic.
What is the role of Hyppocampus in stress cycle and what type of stress does it not affect?
Hippocampus has a calming role in the stress response by providing tonic (constant) inhibition of PVN neurons, thereby reducing HPA activity.
However, the hippocampus has little effect on responses to physical stressors, meaning its role is mostly related to mental or emotional stress.
Prefrontal Cortex role in stress cycle + its 2 regions
Prefrontal Cortex (PFC): Balancing Activation and Inhibition
The PFC has two opposing regions that influence the HPA axis:
1. Ventral PFC: Activates the HPA axis and sympathetic nervous system, increasing stress responses. This is useful when immediate action is required.
2. Dorsal PFC: Suppresses the HPA axis, helping calm the stress response and restore balance after a threat has passed.
Who are endocannabinoids
Endocannabinoids, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are lipid messengers derived from polyunsaturated fatty acids that play critical roles in maintaining homeostasis.
Endocannabinoid System: signaling
Endocannabinoids and Signaling:
- Endocannabinoids act as lipid messengers with autocrine, paracrine, and endocrine functions.
- They use retrograde messaging, meaning that they inhibit signal transduction by traveling from postsynaptic cells back to presynaptic cells, reducing neurotransmitter release.
4. Tonic vs. Phasic Regulation: - The system contributes to tonic inhibition (baseline suppression) of the HPA axis during rest and phasic suppression (acute responses) during stress.
Endocannabinoid System: Regulation of the HPA Axis
Regulation of the HPA Axis:
- AEA plays a distinct role in tonic inhibition of the HPA axis under non-stressful conditions. This occurs via the amygdala, particularly in the basolateral amygdala (BLA), where AEA dampens excitatory input and reduces activation of stress pathways.
- During a psychological stressor, AEA levels rapidly decrease due to its very short half-life. This reduction makes the BLA more sensitive to excitatory input, promoting activation of the HPA axis and downstream stress responses.
- High cortisol levels during stress promote endocannabinoid signaling as part of a feedback mechanism to regulate the stress response.
Endocannabinoid System: Role in Psychiatric Disorders
Role in Psychiatric Disorders:
- Alterations in the endocannabinoid system are implicated in psychiatric conditions like depression. For example, CB1 receptor expression (a receptor for endocannabinoids) and AEA levels are often reduced in depression.
- Interestingly, exercise has been shown to increase AEA levels, particularly in women with depression, suggesting a potential therapeutic role.
Endocannabinoid System: Tonic vs. Phasic Regulation
Tonic vs. Phasic Regulation:
The system contributes to tonic inhibition (baseline suppression) of the HPA axis during rest and phasic suppression (acute responses) during stress.
Endocannabinoid System - how it works
Under normal conditions, AEA ensures that the HPA axis remains suppressed through its action in the amygdala. When a psychological stressor occurs, the drop in AEA removes this inhibition, allowing the HPA axis to activate and mobilize a stress response. This tightly regulated system ensures the body reacts to stress appropriately but also returns to baseline once the stressor is resolved. Dysregulation, such as in depression, can result in an overactive or underactive stress response, further highlighting the importance of the endocannabinoid system in mental health and stress regulation.
The endocannabinoid system - regulation when there is no stress
No Stress:
Under non-stressful conditions, AEA plays a role in maintaining baseline or tonic suppression of the HPA axis.
This is achieved through:
Tonic inhibition of the HPA axis: AEA provides sustained signaling that suppresses the activation of the paraventricular nucleus (PVN) in the hypothalamus, preventing cortisol release.
Gating excitatory input in the BLA (basolateral amygdala): AEA acts as a filter, reducing the excitatory signals entering the BLA. This prevents unnecessary activation of the HPA axis and helps keep the stress response in check during calm states.
The endocannabinoid system - regulation when there is acute stress
During an acute stress event, the role of AEA shifts:
AEA stops gating excitatory input: The levels of AEA rapidly drop due to its short half-life. This removal of AEA’s gating effect increases the sensitivity of the BLA to excitatory input, allowing stress signals to activate the PVN.
PVN activation and cortisol release: The excitatory signals from the BLA promote the activation of the PVN, leading to the release of cortisol, the primary stress hormone, which mobilizes the body’s resources to respond to the stressor.
What are the two types of processes the stress response is terminated through?
- Rapid (non-genomic) feedback process
- Delayed (genomic) feedback process
Rapid Feedback (Non-genomic) - mechanism, outcome and timing
Mechanism: Elevated cortisol levels stimulate the release of 2-AG, an endocannabinoid, within the PVN (paraventricular nucleus of the hypothalamus).
Outcome: This 2-AG release inhibits further production of corticotropin-releasing factor (CRF), effectively dampening the HPA axis activation and ending the stress response.
Timing: This mechanism occurs quickly after the stressor is resolved and helps prevent prolonged cortisol secretion.
Delayed Feedback (Genomic) - mechanism, outcome and relevance
Mechanism: Cortisol binds to glucocorticoid receptors (GR) in corticolimbic structures like the medial prefrontal cortex (mPFC) and hippocampus. These regions are rich in GR, making them highly responsive to cortisol.
Outcome: Enhanced inhibition of the PVN by these corticolimbic structures suppresses the HPA axis over a longer period, providing sustained stress termination.
Relevance: This genomic feedback is particularly effective for psychological stressors and ensures the body returns to homeostasis gradually.
Role of Brain Regions in Stress Termination
Role of Brain Regions in Stress Termination:
1. Basolateral Amygdala (BLA):
During a psychological stressor, AEA levels drop, increasing the sensitivity of the BLA to excitatory input. This promotes HPA activation.
High cortisol levels, however, eventually promote eCB signaling, restoring inhibition of the PVN and ending the stress response.
- mPFC and Hippocampus:
These regions block the excitatory input to the PVN and reestablish inhibition, ensuring the HPA axis is suppressed after the stressor is resolved. - PVN (Paraventricular Nucleus):
The PVN is the key output center for the HPA axis. Its activity is suppressed by the reinstatement of inhibition from regulatory integration centers, marking the termination of the stress response.
