8- Neurophysiology (ANS)- Pt 1.docx

- **ANS (Autonomic Nervous System): General Info** - The ANS is the portion of the nervous system that controls most visceral functions and glandular secretions of the body. - The ANS helps to control: arterial pressure, gastrointestinal motility and secretions, urina...

- **ANS (Autonomic Nervous System): General Info** - The ANS is the portion of the nervous system that controls most visceral functions and glandular secretions of the body. - The ANS helps to control: arterial pressure, gastrointestinal motility and secretions, urinary bladder emptying, body temperature, and more. - Although the ANS is usually defined as a visceral motor system, it has afferent, central, and efferent components. - The target viscera are usually part of reflex pathways that also include afferent pathways and CNS structures like the hypothalamus. - A **ganglion** is a collection of neuronal cell bodies in the PNS. - **ANS: Subdivisions** - The subdivisions of the ANS include the parasympathetic system and the sympathetic system. - The **Parasympathetic system** is known as the "rest and digest system". - The parasympathetic system is responsible for processes that conserve and store energy, as well as controlling the basic visceral functions day-to-day. - For example, breathing while resting, digestion, and waste elimination are controlled by the parasympathetic system. - The parasympathetic system anatomically arises from the cranial nerves and sacral spinal nerves, which is known as the **craniosacral system**. - The parasympathetic system will: - Constrict pupils, airways - Stimulate saliva, stomach activity, gallbladder, intestinal activity - Slow heartbeat - Inhibit release of glucose - Contract the bladder - Promote genital erecting - The **Sympathetic system** is known as the "fight or flight" system, as this system functions when an animal is stressed. - The sympathetic system enables vigorous physical activity with rapid production of energy (ATP). - This system works to increase heart rate, respiration, change in blood flow to active muscles, and pupil dilation for increased vision. - The sympathetic system anatomically arises from the thoracolumbar spinal cord, which is known as the **thoracolumbar system**. - The sympathetic system will: - Dilate pupils - Inhibit salivation, stomach activity, gallbladder, intestinal activity - Increase heartbeat - Relax airways, bladder - Stimulate release of glucose - Secrete epinephrine and norepinephrine - Promote ejaculation and vaginal contraction - Despite the different origins, most viscera receive both sympathetic and parasympathetic input. - These 2 systems work together (usually) in an antagonistic fashion, to maintain homeostasis in the body. - The balance of input from each system determines the organs' functions. - **ANS: Central Components** - The ANS is under the control of the **hypothalamus**, which acts as an integrator. - Afferent and efferent fibers of the ANS travel via the spinal cord and cranial nerves to connect between the CNS (central nervous system) and the target organ. - Hypothalamic control is made by the brainstem (reticular formation) with some influence by the cerebral cortex. - The hypothalamus is part of the **limbic system** which generates autonomic [emotional response]. - The hypothalamus has local receptors (for hormones and osmolarity) and also receive somatic and visceral sensory input directly or indirectly (from the cortex). - **ANS: Preganglionic Neurons** - In the ANS, a preganglionic and postganglionic neuron, in series, connects the CNS with the target organ. - The somatic motor system has only one **LMN** (lower motor neuron) connecting the skeletal muscle and the spinal cord. - The ANS preganglionic neuron has its [cell body] within the CNS, while its [synapse] is with the postganglionic neuron in the peripheral ganglion. - Both sympathetic and parasympathetic system cells bodies of the preganglionic neurons are located in the CNS. - The cell bodies of the **sympathetic preganglionic neurons** form the intermediolateral nucleus of the spinal cord segments T1-L3. - The cell bodies of the **parasympathetic preganglionic neurons** are located in the brain stem and sacral spinal cord (S2 and S3). - **ANS: Postganglionic Neurons** - The postganglionic neuron has its cell body in the peripheral ganglion in the PNS (peripheral nervous system). - The sympathetic system forms the **sympathetic trunk** which is a fusion of several sympathetic ganglia in a chain like form, on each side of the vertebral column. - The postganglionic neurons usually have slow conducting unmyelinated axons. - They innervate smooth muscle (in blood vessels and viscera), cardiac muscle (in the heart) and glandular tissue (visceral or nonvisceral glands). - They can excite or inhibit the target tissue. - There is no generalization to explain whether sympathetic or parasympathetic will cause excitation or inhibition of a particular organ, rather one must understand all separate functions in each organ. - The synaptic buttons are varicosities distributed along the length of the branches. - **Parasympathetic Innervation** - Cranial and sacral preganglionic fibers leave the CNS to synapse in specific ganglia near the target organs. - Thoracic and abdominal visceral organs are supplied by the vagus nerve (cranial nerve 10). - Pelvic visceral organs are supplied by the pelvic nerve. - **Sympathetic Innervation** - Head sympathetic innervation comes from the cranial cervical ganglion. - The heart and lung sympathetic innervation comes from the middle cervical and cervicothoracic ganglia. - The adrenal gland is innervated by a preganglionic neuron. - The abdominal and pelvic visceral organs are supplied by the thoracic and lumbar splanchnic nerves. - Other ganglia innervate blood vessels, sweat glands, and piloerector muscles. - **ANS Neurotransmitters: General Info** - All preganglionic neurons are cholinergic, within both sympathetic and parasympathetic nervous systems. - Cholinergic means that acetylcholine is secreted in the synapse with the postganglionic neuron. - Postganglionic neurons secrete different neurotransmitters. - The [parasympathetic] postganglionic neurons are **cholinergic**, secreting acetylcholine. - The synapse with sweat glands and blood vessels on the skin are cholinergic. - Most [sympathetic] postganglionic neurons are **adrenergic**, secreting norepinephrine. - The synapse with renal vessels are **dopaminergic**. - The [removal of norepinephrine] is done by their reuptake, or diffusion away from the nerve endings, or they are destroyed by enzymes (like monoamine oxidase: **MAO**). - Neurotransmitters released at the synapse will bind to metabotropic or ionotropic receptors at the postsynaptic neuron. - This binding will cause a change in the cell membrane permeability to one or more ions, and it will activate or inactivate second messengers. - **ANS Neurotransmitters: Acetylcholine Mechanism** - Acetylcholine is synthesized in the terminal endings and varicosities of the cholinergic nerve fibers. - Step 1: The enzyme choline acetyltransferase converts acetyl-CoA and choline into acetylcholine. - Step 2: Acetylcholine is stored in a vesicle until it is released. - Step 3: the enzyme Acetylcholinesterase converts acetylcholine into an acetate ion and choline. - Step 4: The choline gets recycled. - **ANS Neurotransmitters: Norepinephrine Mechanism** - Norepinephrine is synthesized in the axoplasm of the varicosities and is stored at secretory vessels. - Step 1: Tyrosine uses hydroxylation to be converted into Dopa. - Step 2: Dopa uses decarboxylation to be converted into Dopamine. - Step 3: Dopamine is transported into vesicles. - Step 4: Dopamine uses hydroxylation to be converted into norepinephrine. - Step 5: Norepinephrine used methylation to be converted into epinephrine. - Norepinephrine conversion into epinephrine will only take place in the adrenal gland. - **Postsynaptic Receptors: Cholinergic** - **Cholinergic receptors** bind to **acetylcholine** and are classified into 2 types: nicotinic and muscarinic. - **Nicotinic receptors** are ligand-gated ion channels found in the autonomic ganglia of both sympathetic and parasympathetic systems. - The channels found in sympathetic and parasympathetic systems are considered to be NN (Neuronal) - Nicotinic receptors are also found at the neuromuscular junction in skeletal muscles, and are considered to be NM (Muscle) - Activation of nicotinic receptors results in EPSPs of the postsynaptic neuron. - Acetylcholine binding to a nAChR (nicotinic acetylcholine receptor) will open its ion channels, allowing for the influx of sodium to the electrochemical gradient. - **Muscarinic receptors** are GPCRs (G-protein coupled receptors) that are found on all effector cells that are stimulated by postganglionic cholinergic neurons or either sympathetic or parasympathetic systems, which activate second messengers. - There are 5 subtypes of muscarinic receptors: M1, M2, M3, M4, M5. - These all signal through Gi or Gq (family of G proteins). - M2 and M4 generate IPSPs. - M1, M3, and M5 generate EPSPs. - The activation of muscarinic receptors will result in EPSPs or IPSPs, depending on the receptor subtype. - For example, M2 in the heart will respond to parasympathetic and decreased heart rate, and contraction force. - For example, M3 in the bronchioles will contract under parasympathetic tone. - **Postsynaptic Receptors: Adrenergic** - **Adrenergic receptors** are located at the synapses between the peripheral target tissues and sympathetic postganglionic neurons that release [norepinephrine] (NE). - Adrenergic receptors are also stimulated by the release of catecholamines from the adrenal glands. - Adrenergic receptors are GPCRs, and they can be further divided into alfa and beta receptors. - **Alfa receptors** have the subtypes: alfa1 (Gq) and alfa2 (Gi). - Alfa receptors induce vasoconstriction of most blood vessels, raising blood pressure. - NE binding to **Alfa1** receptors will activate second messengers, resulting in the release of calcium from the ER, and then either smooth muscle contraction or gland cell secretion. - NE binding to **Alfa2** receptors will reduce cAMP levels, inhibiting the cell, resulting in smooth muscle contraction. - **Beta receptors** have the subtypes: beta1, beta2, beta3 (Gs). - Beta1 in the heart will increase heart rate and contraction force. - Beta blockers will decrease heart rate and prevent arrhythmias. - NE or epinephrine (EPI) binding to beta receptors will activate **adenylate cyclase**, which converts ATP into cAMP, then each beta receptors type will play its own role. - **Beta1** will cause cardiac muscle stimulation and increased tissue metabolism. - **Beta2** will cause relaxation of smooth muscle in respiratory passages and in the blood vessels of skeletal muscle. - **Beta3** will release fatty acids by adipose tissue for metabolic use in other tissues. - **Postsynaptic Receptors: Dopamine** - Dopamine mediates numerus physiological effects in the CNS and at the peripheral target organs. - Dopamine is released by some postganglionic sympathetic neurons synapsing with specific organs, like renal vessels. - Dopamine binds to dopaminergic receptors (which are GPCRs), and this binding will activate different cellular processes, resulting in EPSPs or IPSPs. - Dopamine has a **sympathetic** impact on sweat glands, cardiac and smooth muscle, gland cells, nerve terminals, and renal vascular smooth muscle. - Dopamine has a **parasympathetic** impact on nerve terminals, gland cells, cardiac muscle, and smooth muscle. - Dopamine has a **somatic** impact on skeletal muscle. - Dopamine has the following subtypes: D1, D2, D3, D4, D5.