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Chemical Control of the Brain and Behavior. Ryan Mruczek [email protected] 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

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Chemical control of the brain and behavior l.jpg

Chemical Control of the Brain and Behavior

Ryan Mruczek

[email protected]


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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



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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


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Widespread Systems

  • Neuroendocrine System

  • Autonomic Nervous System

  • Diffuse Modulatory Systems


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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


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Hypothalamus

  • Sits ventral to the thalamus

  • Abuts the third ventricle


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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)


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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


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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)


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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


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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


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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).


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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


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Hypophysiotropic Hormones

Luteinizing hormone (LH)

Follicle-stimulating hormone (FSH)

  • Hypothalamus controls hormone release from anterior pituitary


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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


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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


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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


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Peripheral Nervous System: Autonomic and Somatic


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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.


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ANS Divisions

  • Note distinctions

    • Source

    • Preganglionic nt

    • Postganglionic nt

    • Postgangionic cell bodies

    • Unique targets



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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


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Ionotropic vs. Metabotropic Receptors

Metabotropic Receptor

longer lasting

amplified effects

usually modulatory

Ionotropic Receptor

fast on/off

direct ion flow

signal propagation


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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


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Enteric System

  • Division of ANS

  • Controls digestion

  • As many neurons as spinal cord

  • Operates relatively independently from CNS

    • Supplemental control by ANS


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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


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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


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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


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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


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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


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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!



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