LECTURE 16 AUTONOMIC AND NEUROENDOCRINE SYSTEMS REQUIRED READING

LECTURE 16: AUTONOMIC AND NEUROENDOCRINE SYSTEMS REQUIRED READING: Kandel text, Chapter 49 Autonomic nervous system mediates visceral reflex responses that are involuntary and largely unconscious Autonomic nervous system consists of: 1) Motor neurons which act on smooth muscle, cardiac muscle, and exocrine glands 2) “Preganglionic” CNS neurons whose axons synapse on these motor neurons 3) Visceral sensory neurons 4) Branches and subsets of external-sensing neurons (including somatosensory , olfactory, and retinal) 5) Autonomic postganglionic neurons release neurotransmitters which act through metabotropic receptors on target cells 6) Autonomic responses are coordinated with one another and with behavioral responses and emotions through the hypothalamus in the CNS nicotinic receptors always cholinergic or adrenergic muscarinic or adrenergic receptors

EXAMPLES OF AUTONOMIC FUNCTION Regulation of heartbeat rate Regulation of vascular constriction/dilation Pupil and lens ocular reflexes Exocrine gland secretion Glucose mobilization Sweating and hair follicle erection Bladder filling and emptying Sexual responses Alimentary and bronchial reflexes Gut peristalsis

THREE DIVISIONS OF THE AUTONOMIC NERVOUS SYSTEM Sympathetic nervous system Sympathetic system controls visceral responses that prepare the body for rapid, intense activity, often refered to as FIGHT-OR-FLIGHT REACTION. Responses include accelerated heartbeat, central artery constriction, peripheral vascular dilation, liver glycogen metabolism, & rapid breathing. Other sympathetic responses also work in balance with countering parasympathetic responses to maintain body homeostasis (counteraction to body stress). Parasympathetic nervous system Parasympathetic responses sometimes refered to as the REST-AND-DIGEST STATE. Almost all visceral targets receive both sympathetic & parasympathetic neuronal inputs. Enteric nervous system Enteric neurons form plexuses that surround and extend along the length of the gut, including stomach, small and large intestines. Enteric system activate coordinated contraction of smooth muscles to cause peristaltic constriction of the gut. Most of enteric nervous system functions independently of higher CNS control.

ANATOMY OF SYMPATHETIC & PARASYMPATHETIC NERVOUS SYSTEM Most SYMPATHETIC postganglionic neurons are adrenergic (release E or NE) Most PARASYMPATHETIC postganglionic neurons are cholingeric Site of spinal cord lesion injury can be rapidly assessed by surveying damaged and surviving autonomic reflex responses

ANATOMY OF SYMPATHETIC & PARASYMPATHETIC NERVOUS SYSTEM Generalized “FIGHT” response mediated by sympathetic activation of the adrenal gland, triggering epinephrine secretion into circulation

ANATOMY OF ENTERIC NERVOUS SYSTEM

SENSORIMOTOR CONNECTIONS IN ENTERIC NERVOUS SYSTEM ARE PREDOMINANTLY LOCAL A local circuitry drives peristalsis in the intestines Pressure-sensing neuron senses gut distension PERISTALSIS Acts through interneurons to activate enteric motor neurons with axons projecting rostrally causing squeezing of circular muscle behind the distension Simultaneous inhibition of other motor neurons with axons projecting caudally relaxes downstream circular muscle FOOD DISTENSION PRESSURE SENSING NEURON CIRCULAR MUSCLE MOTOR NEURONS

POST-GANGLIONIC NEUROTRANSMISSION LACKS TYPICAL PRE- AND POST-SYNAPTIC SPECIALIZATIONS Post-ganglionic neuron’s axon terminal lacks clear-vesicle docking machinery. Multiple axonal swellings (varicosities) are sites of neurotransmitter vesicle accumulation. Post-synaptic target (smooth muscle, gland, etc. ) lacks post-synaptic density. Target cell neurotransmitter receptors are broadly distributed on surface. Released neurotransmitter acts diffusely over distances up to 1 mm. Highly branched axons with multiple varicosities enable post-ganglionic neuron to act upon many cells in the target structure.

DIFFUSE TRANSMISSION FROM GANGLIONIC AXONS FACILITATED DISCOVERY OF THE FIRST CHEMICAL NEUROTRANSMITTER Parasympathetic vagus nerve activity slows heartbeat rate, while sympathetic accelerator nerve activity speeds heartbeat rate TWO BEATING FROG HEARTS DISSECTED AND MAINTAINED IN SMALL VOLUME SOLUTION; HEART #1 DISSECTED WITH INNERVATING NERVES ATTACHED HEART #2 DISSECTED WITHOUT NERVES Stimulation of vagal nerve slowed beating of heart #1 After stimulation, transfer of heart #1’s bathing solution to heart #2 slowed its beating Stimulation of accelerator nerve speeds beating of heart #1 After stimulation, transfer of heart #1’s solution to heart #2 sped its beating THEREFORE, NERVE-INDUCED CARDIAC RESPONSES ARE THROUGH SECRETED CHEMICAL NEUROTRANSMITTERS (Vagal transmitter later shown to be ACh, accelerator transmitter is NE)

MECHANISMS OF AUTONOMIC MODULATION OF CARDIAC FUNCTION Parasympathetic release of acetylcholine reduces cardiac output in two ways 1) 2) 2) 3) Muscarinic generation of Gbg directly activates a potassium channel (GIRK) in pacemaker cardiocytes, which slows their depolarization and rate of heartbeat. Muscarinic generation of Gai in heart muscle lowers c. AMP and PKA levels, causing reduced opening of L-type calcium channels, thereby reducing force of heart contraction. Sympathetic release of norepinephrine increases cardiac output in two ways 1) 2) 3) b 1 -adrenergic generation of Gas in pacemaker cardiocytes elevates c. AMP and PKA levels, which reduces the threshold voltage for action potential initiation, thereby increasing rate of heartbeat. b 1 -adrenergic elevation of c. AMP and PKA in heart muscle increases opening of L-type calcium channels, thereby increasing force of heart contraction.

SENSORY INPUTS TO AUTONOMIC FUNCTION Our bodies sense deleterious changes and undertake automatic responses to maintain homeostasis. Sensory inputs eliciting autonomic responses include: 1) 2) External sensations which trigger corrective reflexes Examples: a) Ocular reflexes -- pupil dilation or constriction in response to light, 3) lens stretching to adjust focus 4) 5) 6) http: //library. med. utah. edu/kw/hyperbrain/anim/reflex. html b) Painful laceration -- vasoconstriction to limit blood loss sympathetic activation of coordinated fight/flight responses 2) Visceral sensations induce homeostatic responses 3) Examples: 4) a) Opposing sympathetic/parasympathetic control of heartbeat and blood pressure -5) If sympathetic activity drives heartbeat and artery constriction too much, 6) pressure-sensitive sensory afferents in the aorta trigger the baroreceptor reflex, 7) which includes parasympathetic vagal input to heart and induction of 8) arterial dilation 9) http: //highered. mcgraw-hill. com/sites/0072507470/student_view 0/chapter 21/animation__baroreceptor_reflex_control_of_blood_pressure. html 10) Reciprocally, pressure-sensitive sensory afferents in the cardiac right atriam sense distention 11) triggering the right atrial reflex, by which sympathetic accerelerator nerve firing speeds rate b) Irritants to oronasal cavities act through parasympathetic ganglia c) to trigger nasal and lacrimal glandular secretions

PREGANGLIONIC FIBERS RELEASE SMALL MOLECULE AND PEPTIDE NEUROTRANSMITTERS TO ELICIT COMPLEX GANGLIONIC NEURON RESPONSES Single or low-frequency preganglionic firing releases Ach which activates nicotinic receptors triggering fast EPSP in postganglionic neuron. High-frequency stimulation releases more Ach and LHRH peptide. The complex postganglionic response consists of fast EPSP, slow IPSP mediated by muscarinic receptor activation of GIRKs, and delayed EPSP resulting from LHRH binding to peptidergic receptors.

SENSORY PATHWAYS OF SYMPATHETIC AND PARASYMPATHETIC SYSTEMS PASS LOOP THROUGH BRAIN STEM, BUT ALSO PROJECT TO CONSCIOUS CORTICAL AREAS ASCENDING VISCERAL SENSORY PATHWAYS DESCENDING AUTONOMIC RESPONSE PATHWAYS

HYPOTHALAMUS COORDINATES PHYSIOLOGY AND BEHAVIOR IN RESPONSE TO VISCERAL SENSORY INPUTS EXAMPLE: BLOOD OSMOLARITY HOMEOSTASIS VISCERAL SENSORY INPUTS Blood pressure Blood osmolarity HYPOTHALAMUS COORDINATED OUTPUTS Autonomic -- action on smooth muscles in central and peripheral vasculature Behavioral -- conscious thirst which drives search for fluid intake Endocrine -- secretion of vasopressin into blood, which promotes water resorption by kidneys

HYPOTHALAMUS CONTROLS HORMONE RELEASE FROM PITUITARY GLAND BOTH DIRECTLY AND INDIRECTLY