Chemical Control of the Brain and Behavior

1. Chemical Control of the Brain and Behavior Ryan Mruczek Ryan_Mruczek@Brown.edu

2. Point to Point LGN to V1 Fast Onset Short Duration Specific Disruption leads to specific sensory/motor deficit, such as a blind spot Widespread Hormone released into blood stream Expanded in space and time Non-Specific Slow Onset and Prolonged Effects Disruption has more global consequences Types of Communication

3. Point to Point vs. Widespread

4. Widespread Systems • Neuroendocrine System • Maintain homeostasis through controlled hormone release • Autonomic Nervous System • Coordinates the response of all body organs in response to environment • Diffuse Modulatory Systems • Small groups of neurons that send axons to many thousands of postsynaptic cells throughout the brain

5. Widespread Systems • Neuroendocrine System • Autonomic Nervous System • Diffuse Modulatory Systems

6. Neuroendocrine System • Hypothalamus controlled hormone release • Control organs to maintain homeostasis • Monitors bodies internal environment • Temperature • Salt and acidity of blood • Glucose concentrations • Blood pressure and heart rate • Sleep/Wake cycle (Circadian Rhythm) • Keeps within small physiological working range • Reproductive behaviors

7. Hypothalamus • Sits ventral to the thalamus • Abuts the third ventricle

8. Hypothalamic Zones • Lateral/Medial • Connections with brainstem and telencephalon • More on this structure later in the course • Periventricular Zone (next to the third ventricle) • Superchiasmatic nucleus • Control autonomic nervous system • Neuroendocrine System (hormone communication)

9. Pituitary • Below the hypothalamus • Connected by pituitary stalk • Neurosecretory neurons project to pituitary • Allows hypothalamus to communicate with the rest of the body • Two Divisions of Pituitary • Anterior • Posterior

10. Posterior Pituitary • Magnocellular neurosecretory cells of hypothalamus • Directly release hormones into bloodstream • Neurons act like glands • Neurotransmitter (peptides; neurohormones) act like hormones • Oxytosin • Vasopressin (ADH)

11. Oxytocin • Facilitates birth • causes uterus to contract • Stimulates release of milk from mammary glands • In response to sensory stimulus (visual, auditory, somatic) • Suppressed during anxiety • Also found in men and non-pregnant women so must have other functions as well

12. Vasopressin (ADH) • a.k.a. Anti-Diuretic Hormone (ADH) • Regulates blood volume • Low blood vol, high [salt], low blood pressure • Detected by circulatory system and hypothalamus • Hypothalamus releases vasopressin • Kidney senses vasopressin and increases water retention and lowers urine production • Kidney also communicates with brain

13. 2-Way Communication • Low blood vol. and high [salt] lead kidney to release renin • Renin converts Angiotensin to Angiotensin I • Angiotensin I breaks down to Angiotensin II • Angiotensin II • Kidney and blood vessels increase blood pressure • Detected by subfornical organ in brain (no blood brain barrier) and leads to vasopressin release and increase thirst (behavior).

14. Anterior Pituitary • Acts as a gland, not part of brain. • Synthesize and secrete many hormones • But hypothalamus is “master gland” • parvocellular neurosecretory cells tell anterior pituitary what to do • Release hypophysiotropic hormones which cause increase/decrease secretion of pituitary hormones into bloodstream

15. Hypophysiotropic Hormones Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) • Hypothalamus controls hormone release from anterior pituitary

16. Cortisol Self regulating: Inhibit more CRH release • Stress response • Hypothalamus releases CRH (corticotropin releasing hormone) • Anterior pituitary releases adrenocorticotropic hormone (ACTH) • a.k.a corticotropin • Adrenal glands sit on kidney • Adrenal medulla inside • Adrenal cortex outside • Produces cortisol in response to ACTH • Cortisol mobilizes energy storages and inhibits immune system CRH

17. Neuroendocrine Summary • Hypothalamus (periventricular zone), pituitary and the released hormones form the neuroendocrine system • Neurosecretory neurons controls the release of hormones from the pituitary gland • Posterior pituitary: direct release of neurohormones • Anterior pituitary: releasing factors control hormonal release • Periventricular zone also controls the autonomic nervous system

18. Autonomic Nervous System (ANS) • Widely distributed network of neurons controlling highly coordinated, automatic functions • Thermoregulation • Fluid Balance • Salt and acidity balance • Food Intake and Energy Regulation • Glucose storage and mobilization • Cardiovascular Reflexes • Blood pressure, vasculature, heart rate, blood volume • Circadian Rhythm • Stress response (fight/flight) • Sexual responses

19. Peripheral Nervous System: Autonomic and Somatic

20. Divisions of the ANS • Sympathetic • Fight or flight response • Mobilize energy source and prepare body to handle stress • Parasympathetic • Active during rest, digestion, energy storage, immune response • Antagonistic functions • Divisions in competition with each other, but more of a balance between the two systems at any one time.

21. ANS Divisions • Note distinctions • Source • Preganglionic nt • Postganglionic nt • Postgangionic cell bodies • Unique targets

22. ANS Division Summary

23. ANS as Widespread System • Looks point to point, but activity is expanded in space and time • Typically, many pathways active at one time, especially for sympathetic response • Long lasting effects, even after initial stimulus is removed (partially due to nt receptors) • Large number of targets controlled by small number of cells • Responds to circulating hormones • Epinephrine (adrenaline) released from adrenal medulla and activates sympathetic nervous system throughout body

24. Ionotropic vs. Metabotropic Receptors Metabotropic Receptor longer lasting amplified effects usually modulatory Ionotropic Receptor fast on/off direct ion flow signal propagation

25. Drug Interactions of the ANS • Drugs typically interact with specific neurotransmitter receptors and either mimic (agonist) their effects, or inhibit (antagonist) normal effects. • Sympathomimetic – bias towards sympathetic division • Parasympathomimetic – bias towards parasympathetic division • Atropine: block muscarinic ACh • General block of parasympathetic system (sympathomimetic) • Counter act poison gas: organophosphates block acetylcholinesterase • Symptoms look like overactive parasympathetic system • Selectivity of drugs • Place drug where you want it • Dilate pupils with atropine drops • Different receptor subtypes in different organs • Lower heart rate by blocking NE with propranolol • But also blocks NE receptors in lungs; especially bad for asthmatics • Block heart NE receptor (B1) only: atenolol • Stimulate lung NE receptor (B2) only: albuterol

26. Enteric System • Division of ANS • Controls digestion • As many neurons as spinal cord • Operates relatively independently from CNS • Supplemental control by ANS

27. Diffuse Modulatory Systems (DMS) • Control behaviors that require the coordination of many brain areas • Sleep/wake cycles • Attention and arousal • Learning and memory • Motivation and reward (and addiction) • Typically modulate normal activity • Increase/decrease neural excitability • Adjust synchrony and rhythms

28. DMS General Anatomy • Source • Small core of neurons, typically in brainstem • Projections • Send each axon to more than 100,000 postsynaptic neurons • Widely divergent • One axon can have branches in cortex and cerebellum • Targets • Many parts of cortex, spinal cord, cerebellum, thalamus… • Synapses • Non-specific • Release nt into extracellular fluid, which can diffuse to many surrounding neurons

29. Noradrenergic Locus Coeruleus • Many functions because of very widespread connections • Attention and arousal • Sleep/wake cycles • (Learning and memory, pain, metabolism, mood) • Most active in the presence of new or unexpected, non-painful stimuli • NE may make neurons more responsive and easier to activate • Least active during rest

30. Seretonergic Raphe Nuclei • Caudal nuclei (medulla) innervate spinal cord and are involved in pain modulation • Rostral nuclei (pons and midbrain) similar to locus coeruleus • Widespread cortical and subcortical projections • Most active when animal is awake and aroused • Least active during sleep • NE and 5-HT DMS form the ascending reticular activating system

31. Dompaminergic DMS • 1. Substantia nigra to striatum • Facilitate initiation of voluntary movements • Damage leads to Parkinson’s Disease • 2. Ventral tegmental area to frontal cortex and limbic system • “Reward” system that reinforces adaptive behaviors • Also involved in addiction and some psychiatric disorders

32. Cholenergic DMS • 1. Basal forebrain complex • Medial septal nucleus to hippocampus • First cells to die in Alzheimer’s disease thus linked to cognitive funcitons, learning and memory • 2. Pontomesen-cephalotegmental complex • Pons and midbrain nuclei to thalamus • Regulates excitability of thalamic relay neurons • Perfect position to control arousal and attention!

33. DMS Summary