Stress and Emotion. Stressors are things that challenge homeostasis -- these challenges may be real or merely anticipated

Transcription

1 Stress and Emotion 1 Stressors are things that challenge homeostasis -- these challenges may be real or merely anticipated Stress responses are what the body does about it 2 1

2 Two broad stressor categories 1. Interoceptive/visceral stressors a) True challenge to body homeostasis b) Cognitive awareness not necessary c) Usually no learning/experience required 2. Neurogenic/psychological stressors a) Requires cognitive awareness b) Perceived challenge may be immediate or anticipated c) Past experience/learning often required 3 Stress Responses Overall effect is to increase catabolic and decrease anabolic processes Endocrine components Autonomic components Behavioral components Hypothalamus 4 2

3 Stress Responses Overall effect is to increase catabolic and decrease anabolic processes Endocrine components Autonomic components Behavioral components PVN 5 * The Hypothalamic PVN 6 3

4 Stress-related PVN components Endocrine neurons (green) that make/ release CRH Corticotropicreleasing hormone Pre-autonomic neurons that project to brainstem and spinal autonomic motor neurons (red) 7 7 Inputs to the PVN PVN 8 4

5 Forebrain cortex hippocampus amygdala, bed nucleus septum thalamus Inputs to the PVN Other Hypothalamic n. motivational and behavioral states (LH) interoceptive context Circumventricular blood-borne signals PVN Brainstem visceral sensory somatic nociceptive special sensory 9 Two-System View of the Stress Response 10 Kolb and Whishaw 2nd Ed. 5

6 Two-System View of the Stress Response Stressor brain PVN Anterior pituitary Sympathetic nervous system Adrenal cortex Adrenal medulla (chromaffin cells) Glucocorticoids (cortisol in humans, corticosterone in rats) into bloodstream Epinephrine (E) & NE into bloodstream a.k.a. adrenaline 11 Spinal cord = Acetylcholine Sympathetic preganglionic fiber = Norepinephrine = Epinephrine Adrenal medulla Sympathetic postganglionic fiber Blood Sympathetic limb of stress response Target organs 12 6

7 CRF endocrine neuron Endocrine (slower acting) limb of stress response Systemic arterial inflow Hypothalamus Median eminence Anterior pituitary Hypothalamic-hypophyseal portal system 13 System Venous outflow containing ACTH Posterior pituitary Adrenocorticotropic hormone (ACTH) secretory cell (a.k.a. corticotropes ) = Anterior pituitary hormone Hypothalamus Anterior pituitary Posterior pituitary Corticotropes in anterior pituitary TSH ACTH Adrenal cortex Cortisol Cortisol = glucocorticoid (GC) GR = glucocorticoid receptors GR-mediated genomic and cell actions 14 7

8 Glucocorticoids (GC) cortisol (humans), corticosterone (rats, mice) Synthesized from cholesterol in response to ACTH-induced receptor activation of cells in adrenal cortex - via increased adenylate cyclase, increased camp, activation of enzymes - cortisol cannot be stored in vesicles (highly lipophilic) - In circulation, only 10% of GC is free, 90% bound to corticosteroid-binding globulin (CBG, a.k.a. transcortin ) to buffer against wild fluctuations MANY ROLES, including: carbohydrate metabolism - increase and maintain circulating glucose levels (hence the term GC ) via various effects on liver, muscle, fat (adipose tissue) 15 Plasma membrane Cytoplasm of target cell Figure 18.5 Page 676 Nucleus Cortisol acts on intracellular receptors that modify the cellular genome H = Free lipophilic hormone (i.e., GC) HRE = Hormone response element (prom. regions) R = Lipophilic hormone receptor (i.e., GR) mrna = messenger RNA (many genes) 16 8

9 17 Negative feedback control of the hypothalamic pituitary adrenal (HPA) axis Effect of adrenalectomy? Dexamethasone suppression test Figure

10 Major inputs to CRH neuroendocrine neurons 21 The Amygdala and Emotional Responses Emotional State = physiological state Product of endocrine, autonomic, somatic output systems ( emotional motor system ) Product of innate and learned responses to the world; most responses occur subconsciously Feelings are constructed from sensory feedback to the brain about emotional state reflect a context-dependent cognitive process shaped by exteroceptive cues, experience 20 10

11 Modern Theories of Emotion Schacter & Schacter, Damasio, Arnold, Prinz Strongly influenced by James-Lange theory 21 Embodied Appraisal Theory (Jesse Prinz) Feelings reflect an embodied appraisal of one s physiological emotional state within a real (or anticipated) environmental context The amygdala intervenes between emotional state expression (emotional motor system) and cortical/cognitive processing of feelings The amygdala mediates dynamic interactions between cortical and subcortical processes that are initiated by sensory input and further modulated by sensory feedback 22 11

12 23 The Limbic Lobe (forms a rim, limbus, around corpus callosum and diencephalon) 24 12

13 The expanded Limbic Lobe 25 Nuclei of the rat amygdaloid complex P. SAH et al. Physiol Rev 2003;83:

14 Summary of inputs to the amygdaloid nuclei P. SAH et al. Physiol Rev 2003;83: Neuromodulatory inputs (e.g., ACh, 5-HT, NE) have been omitted for clarity. How do stimuli/events attain emotional significance? Some emotional responses are automatic, INNATE Most emotional responses are LEARNED (conditioned); thus, they depend on experience emotional learning: construction of implicit memories linking a situation or event to an emotional body state can be conscious, but often is subconscious Modulated by arousal 28 14

15 AROUSAL via ACh, 5-HT, NE modulatory inputs, including VISCERAL SENSORY FEEDBACK from the caudal medulla, GRmediated signaling from circulating corticosterone 29 Arousal is a major aspect of many learning theories and is closely related to other concepts such as anxiety, attention, agitation, stress, and motivation. Memory, performance efficiency (arousal) Yerkes-Dodson Law Robert M. Yerkes and John D. Dodson, The Relation of Strength of Stimulus to Rapidity of Habit-Formation (1908) Journal of Comparative Neurology and Psychology 18:

16 Summary of inputs to the amygdaloid nuclei P. SAH et al. Physiol Rev 2003;83: Neuromodulatory inputs (e.g., ACh, 5-HT, NE) have been omitted for clarity. Basolateral Amygdala (BLA) BLA neurons are cortical-like (glutamatergic) Sensory convergence inputs from medial PFC, multimodal sensory cortices, hippocampus (context/place); high road Direct inputs from thalamus ( low road ; unfiltered) single BLA neurons respond to diverse sensory stimuli receives robust noradrenergic (NA) inputs from brainstem (increased NA activation by arousal) projects into the central amygdala 32 16

17 Emotional Learning 33 Kolb & Whishaw Peri-Event Time Histogram of LA neural responses (a) PETH showing response of an LA neuron to unpaired shock pulses that were delivered prior to CS-US pairing (arrows indicate the times of shock pulse delivery). (b) PETH showing response of the same neuron to auditory CS pips delivered before (gray bars) and after (black bars) CS-US pairing (horizontal gray bar indicates the time and duration of the 250-ms auditory pip CS). This cell showed significant conditioned enhancement of its response to the CS and was also shock-responsive. Bin size is 10 ms for all PETHs. BLAIR: Ann N Y Acad Sci (2003) 985:

18 35 outputs 36 18

19 Functional model of the basic pathways and synaptic plasticity proposed to underlie fear conditioning. Sensory stimuli about the CS and US converge on single neurons within the lateral nucleus of the amygdala. Via LTP, this convergence enhances EPSPs evoked by the CS, which enhances LA signaling to the CeA (directly and indirectly). CeA outputs control behavioral, autonomic, and HPA axis responses to both the US and the CS. P. SAH et al. Physiol Rev 2003;83: Summary of inputs to the amygdaloid nuclei P. SAH et al. Physiol Rev 2003;83: Neuromodulatory inputs (e.g., ACh, 5-HT, NE) have been omitted for clarity. 19

20 Central Amygdala (CeA) CeA neurons are striatal-like (1 o GABAergic) Response divergence Projects to autonomic motor neurons Projects (indirectly) to endocrine CRH neurons in PVN of hypothalamus (the apex of the HPA axis) Projects to central gray, somatic motor control centers Visceral sensory feedback from caudal medulla (NA inputs from A1, A2 cell groups) 39 Pavlovian Fear Conditioning Emotional URs and CRs are outputs of the central n. of amygdala K&S, Figure 50-9 Response Divergence 40 20