Lecture 7: Stress, HPA Axis and Hypothalamus
Link memory and hippocampus to broader limbic system. In particular, how hippocampal memory,
and memory in other parts of the limbic system (e.g. amygdala), is modulated by stress responses
and how that links into activation of the HPA axis.
The fundamentals of the stress response and the hypothalamic-pituitary-adrenal (HPA) axis
Where do limbic cortical structures, such as the hippocampus, fit into this system?
Walter Cannon (1915)
• Stress is a stimulus that challenges the organisms’ homeostasis
o Homeostasis = sum of mechanisms maintaining the organism in a steady state
o Canon is the father of the sympathetic NS ‘fight or flight’ response
o Emphasised homeostasis in the organism – homeostasis is the basis of motivation
§ When organism homeostasis is imbalanced, organism tries to return to
equilibrium/homeostasis point/ physiologically stable point
§ threat imbalances homeostasis (e.g. fight or flight response) à
organisms tries to return to origin point
Conclusion: Never used the word ‘stress’ (not invented yet), but talked about how all the
mechanisms needed to keep an organism at homeostasis where a demand/drain on the organism.
This set up thinking about stress for the psychologist (Seyle) who coined the term in how we use
‘stress’ today. Stressors result in an imbalance to homeostasis that tries to be corrected in
organisms.
Hans Selye (1956)
• Introduced the psychological concept, the General Adaptation Syndrome (GAS) – there is a
general response produced by an organism of all sorts of different types of challenges
• Physiological tests – injected ground organs into other animals; how will the animal deal
with this imbalance in physiological homeostasis
o He did not see a discrete set of responses per injected organ, but instead one
particular type of response that came up regardless of extract à adrenal response
o He noticed that the adrenal glands always show a response to plasma-induced
homeostasis imbalance/ all sorts of physiological stressors
§ Injecting extracts of animal organs, hunger, thirst, temperature, dropped
blood sugar
o All these physiological challenges create a non-specific response; the organisms
has a general response mechanism to deal with all of these different stressors
• Selye introduced the term ‘stress’ to mean all of these different types of physiological
challenges that imbalance the organisms’ homeostasis, requiring the organism to adapt to
return to origin point
o “Stress is the sum of non-specific response of an organisms to any challenge”
• Last stage of model is exhaustion, where adaption response to stressor falls away, when too
much stress is applied
, o Something we still think about in modern neuroscience
o Animal can adapt to stressor for a certain amount of time and to a certain
physiological level, beyond that you become exhausted
What is stress?
• A real or interpreted threat to the physiological or psychological integrity of an individual
that results in physiological and/or behavioural responses
There are two key elements:
• Separation of stress in 3 steps:
o Input (stressor, as emphasised by Cannon definition)
o Processing by the organism
o Output (stress response, as in Seyle definition)
• Modern definition introduces of subjectivity of the threat perception
o Not just simple physiological stressors (e.g. thirst/hunger), but also perceived threat
to psychological integrity (e.g difficult interpersonal relationships )
Our modern understanding of stress combines Cannon’s and Seyle’s theories. We separate both
stressors and output stress response into two phases.
Two paths to trigger the stress response:
1. Systemic stressor
a. Physical injury
b. Physical exertion
i. These systems act via direct monosynaptic relay to PVN
ii. Monitored by brainstem function
Systemic stressors have a direct relay to the paraventricular nucleus of the hypothalamus (PVN):
subfornical organ, area postrema
2. Psychogenic stressor
a. Time pressured task
b. Interpersonal conflict
i. Multisynaptic processing and indirect relay to PVN
ii. Processed by limbic forebrain structures à hypothalamic PVN
Psychogenic stressors have indirect relay via limbic forebrain structures to the PVN
PVN (hypothalamus) is gateway structure that takes in input from the body and brain; processes the
input and, where necessary, initiates the stress response
• These systemic stressors are monitored by brainstem function (e.g. can monitor blood
sugar, indications of injury in blood stream) and project directly to PVN when those warning
signals are picked up
PVN is always key gateway in relieving a stress response
Link memory and hippocampus to broader limbic system. In particular, how hippocampal memory,
and memory in other parts of the limbic system (e.g. amygdala), is modulated by stress responses
and how that links into activation of the HPA axis.
The fundamentals of the stress response and the hypothalamic-pituitary-adrenal (HPA) axis
Where do limbic cortical structures, such as the hippocampus, fit into this system?
Walter Cannon (1915)
• Stress is a stimulus that challenges the organisms’ homeostasis
o Homeostasis = sum of mechanisms maintaining the organism in a steady state
o Canon is the father of the sympathetic NS ‘fight or flight’ response
o Emphasised homeostasis in the organism – homeostasis is the basis of motivation
§ When organism homeostasis is imbalanced, organism tries to return to
equilibrium/homeostasis point/ physiologically stable point
§ threat imbalances homeostasis (e.g. fight or flight response) à
organisms tries to return to origin point
Conclusion: Never used the word ‘stress’ (not invented yet), but talked about how all the
mechanisms needed to keep an organism at homeostasis where a demand/drain on the organism.
This set up thinking about stress for the psychologist (Seyle) who coined the term in how we use
‘stress’ today. Stressors result in an imbalance to homeostasis that tries to be corrected in
organisms.
Hans Selye (1956)
• Introduced the psychological concept, the General Adaptation Syndrome (GAS) – there is a
general response produced by an organism of all sorts of different types of challenges
• Physiological tests – injected ground organs into other animals; how will the animal deal
with this imbalance in physiological homeostasis
o He did not see a discrete set of responses per injected organ, but instead one
particular type of response that came up regardless of extract à adrenal response
o He noticed that the adrenal glands always show a response to plasma-induced
homeostasis imbalance/ all sorts of physiological stressors
§ Injecting extracts of animal organs, hunger, thirst, temperature, dropped
blood sugar
o All these physiological challenges create a non-specific response; the organisms
has a general response mechanism to deal with all of these different stressors
• Selye introduced the term ‘stress’ to mean all of these different types of physiological
challenges that imbalance the organisms’ homeostasis, requiring the organism to adapt to
return to origin point
o “Stress is the sum of non-specific response of an organisms to any challenge”
• Last stage of model is exhaustion, where adaption response to stressor falls away, when too
much stress is applied
, o Something we still think about in modern neuroscience
o Animal can adapt to stressor for a certain amount of time and to a certain
physiological level, beyond that you become exhausted
What is stress?
• A real or interpreted threat to the physiological or psychological integrity of an individual
that results in physiological and/or behavioural responses
There are two key elements:
• Separation of stress in 3 steps:
o Input (stressor, as emphasised by Cannon definition)
o Processing by the organism
o Output (stress response, as in Seyle definition)
• Modern definition introduces of subjectivity of the threat perception
o Not just simple physiological stressors (e.g. thirst/hunger), but also perceived threat
to psychological integrity (e.g difficult interpersonal relationships )
Our modern understanding of stress combines Cannon’s and Seyle’s theories. We separate both
stressors and output stress response into two phases.
Two paths to trigger the stress response:
1. Systemic stressor
a. Physical injury
b. Physical exertion
i. These systems act via direct monosynaptic relay to PVN
ii. Monitored by brainstem function
Systemic stressors have a direct relay to the paraventricular nucleus of the hypothalamus (PVN):
subfornical organ, area postrema
2. Psychogenic stressor
a. Time pressured task
b. Interpersonal conflict
i. Multisynaptic processing and indirect relay to PVN
ii. Processed by limbic forebrain structures à hypothalamic PVN
Psychogenic stressors have indirect relay via limbic forebrain structures to the PVN
PVN (hypothalamus) is gateway structure that takes in input from the body and brain; processes the
input and, where necessary, initiates the stress response
• These systemic stressors are monitored by brainstem function (e.g. can monitor blood
sugar, indications of injury in blood stream) and project directly to PVN when those warning
signals are picked up
PVN is always key gateway in relieving a stress response
