STRESS AND PLASTICITY

What is allostasis?
• Homeostasis implies that an organism
remains within a certain range of
physiological parameters to maintain stable
function.
• Allostasis implies that an organism
constantly varies and adjusts physiological
parameters to maintain stable function.
• Allostasis is an alternative hypothesis that
takes environmental stimuli into account.
• Allostasis implies that homeostasis is an
unrealistic goal. (a pipe dream)
“Homeostasis emphasized that the body’s internal
environment is held constant by the self-correcting (negative
feedback) actions of its constituent organs. Allostasis
emphasizes that the internal milieu varies to meet perceived
and anticipated demand. This variation is acheieved by
multiple, mutually reinforcing neural and neuroendocrine
mechanisms that override the homeostatic mechanisms. The
allostatic model, in emphasizing the subordination of local
feedbacks to control by the brain, provides a strong
conceptual framework to explain social and psychological
modulation of physiology and pathology.”
Peter Sterling and Joseph Eyer, 1988
 Allostatic Load
• Prolonged neurochemical imbalance has
negative consequences (pathology in
extreme cases) for normal neural function.
This is called the "allostatic load" - the cost
to the brain and body of continual allostatic
response.
 Examples of Allostatic Load:
• Chronic stress effects on spatial memory
• Reward dysregulation during drug addiction
• Affective memory consolidation during
stress
• Stress effects on working memory
 Why Stress and Allostasis?
• “Allostasis is a paradigm to explain arousal
pathology” Sterling & Eyer, 1988
• Chronic stress leads to arousal pathology -
where there is constant deviation from
regular physiological parameters.
• The neural systems involved in control of
allostasis are the ones regulating stress
pathology.
 Stress:
• Somatic - responses to noxious demands
upon the body.
• Social/psychological - responding to
various external/internal demands upon the
brain and body.
 Allostasis is a system wide
phenomenon
• All the neural systems discussed are
interconnected.
• Allostatic load pathology stemming from
dysregulation of any one of these systems
will also produce a vulnarability to other
allostatic pathologies.
• Extended Amygdala is an integral part of all
these circuits and is well located to drive the
CNS stress response.
 Extended Amygdala
• Theoretical construct based on structural
and functional similarity
– Amygdala
– Bed Nucleus of Stria Terminalis (BNST or
BST) as an extension of central nucleus of
amygdala (CeA)
– Shell of Nucleus Accumbens (NAcc) as an
extension of the medial nucleus of amygdala
 Examples of Allostatic Load
Discussed Today:
• Chronic stress effects on spatial memory
– Link to Hippocampal Atrophy
• Reward dysregulation during drug addiction
– Basal Ganglia and Nucleus Accumbens
• Affective memory consolidation during
stress
– Amygdala based function
• Stress effects on working memory
– PreFrontal cortex based function
 Some of the Neuromodulators
Involved:
• Corticotropin Releasing Factor (CRF) -
neurochemical instigator of CNS and ANS
stress response.
• Dopamine (DA) - involved in
reward/motivational mechanisms.
• Norepinephrine (NE) - involved in arousal
mechanisms.
 Changes in NT’s during
Allostasis.
• CRF - Upregulated globally.
• DA - Downregulated selectively with local
sensitization of receptors.
• NE - Upregulated globally.
CRF Receptors
Interactions of CRF/NE
Effects of CRF
Role of Coeruleus
 Why Drug Addiction and
Allostasis?
• Too much of a rewarding stimulus gives rise
to an arousal pathology.
• Reward dysregulation is a change in
motivational salience.
• The process of reward dysregulation is
allostatic in nature since there is a persistent
deviation from normal neural function.
 Conclusions:
• NE and CRF potentiating allostatic load.
• Opposite effects of stress at cortical v.
subcortical levels.
• Interconnectedness of neural circuits
involved in allostasis.
• Implications for Mood and Anxiety
Disorders.