STRESS AND PLASTICITY What is allostasis Homeostasis implies

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 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 (Ce. A) – 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 – Pre. Frontal 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.