Neurons and Nervous System

Neurons, Nervous System, Synapse

• The central nervous system (CNS) consists of the brain and spinal cord.
• The peripheral nervous system (PNS) includes all the nerves arising from and leading to the CNS, comprising sensory receptors, sensory neurons, motor neurons, and effectors.
• Sensory neurons carry nerve impulses to the CNS.
• Motor neurons carry nerve impulses away from the CNS.
• The PNS can be divided into somatic sensory, somatic motor, visceral sensory, and visceral motor categories, based on body region served and nerve signal direction.
• Glial cells are supporting cells in the nervous system that aid neurons
  • There are four types in the CNS: microglia, oligodendrocytes, astrocytes, and ependymal cells
  • Two types are present in the PNS: satellite cells and Schwann cells.
• Dendrites carry signals towards the cell body, while axons carry signals away.
• Association/interneurons are located entirely within the CNS and integrate nervous system functions.
• Skeletal muscle motor commands use a monosynaptic synapse, involving one neuron issuing from the CNS.
• The visceral motor division of the PNS uses two synapses, involving two neurons from the CNS, one synapse in the autonomic ganglion, and another in the effector.
• Neurons can be classified into unipolar (or pseudounipolar), bipolar, and multipolar based on the number of processes extending from the cell body.
• Bundles of axons in the PNS are nerves, while in the CNS, they are tracts.
• Astrocytes and ependymal cells support the blood-brain barrier and form cerebrospinal fluid (CSF) in the CNS.
• Myelinated axons are covered by Schwann cells with high lipid content, forming a myelin sheath
  • Nonmyelinated axons are internalized by Schwann cells but remain unmyelinated within longitudinal channels.
• Multiple sclerosis involves autoimmune-mediated damage to the myelin sheath, causing demyelination and affecting nerve impulse transmission in the brain and spinal cord.
• Schwann cells form a regeneration tube, directing and stimulating cut neuron ends to reconnect due to growth factors
  • Oligodendrocytes in the CNS do not form regeneration tubes and do not secrete growth factors, hindering neuronal growth.

Supporting Cells and Membrane Potential

• Astrocytes, the most abundant support cells in the CNS, have several functions: forming Bblood-brain barrier, taking up potassium from the ECF to maintain ionic balance, taking up glucose from the blood for neuronal ATP production, recycling neurotransmitters from axon terminals, providing structural support, and forming synapses.
• Resting membrane potential is the voltage difference across the plasma membrane of a resting cell, resulting from unequal ion distribution due to membrane impermeability, the Na+/K+ pump, and negatively charged proteins inside the cell.
• The average resting membrane potential is -70 mV, negative due to the inside of the cell being more negative than the outside.
• The Na+/K+ pump moves 3 Na+ ions out of the cell for every 2 K+ ions into the cell.
• At rest, neurons have high K+ concentration inside (balanced by negatively charged proteins) and high Na+ concentration outside (balanced by high Cl-).
• The establishment of membrane potential is influenced by membrane permeability to ions, the Na+/K+ pump, and the presence of negatively charged proteins inside the cell.
• In a polarized cell membrane, Na+ concentration is high outside the cell, and K+ concentration is high inside the cell.
• Muscle and neurons are the two tissue types exhibiting cell excitability.
• Depolarization occurs when the membrane potential becomes less negative, with Na+ influx causing the resting membrane potential to rise and the inside of the cell becoming more positive.
• Repolarization is caused by the closing of Na+ channels and the opening of K+ channels, which initiate K+ efflux.
• Threshold potential is the membrane potential level to which a membrane must be depolarized to initiate an action potential.
• An action potential is a transient event where the membrane potential rapidly rises (Na+ influx) and falls (K+ efflux), creating an electrochemical signal.
• Hyperpolarization is a change in the cell's membrane potential, making it more negative due to excess K+ efflux or Cl- influx.
• Hyperpolarization inhibits the generation of action potential because it makes the cell membrane potential more negative, requiring a stronger stimulus to reach threshold.
• Potassium ions have leaky K+ channels (always open) and voltage-gated K+ channels in axons.
• Axons have only voltage-gated Na+ channels that are closed at rest.
• The Na+/K+ ATPase transporter re-establishes resting potential after hyperpolarization by pumping Na out and K in.

Action Potentials and Synapses

• Action potentials follow an all-or-none principle, generated when membrane potential reaches threshold, with stimulus strength coded by the frequency of action potentials.
• Refractory periods are the time needed for neuron recovery before responding to another stimulus
  • Absolute refractory period: Na+ channels are fully open
  • Relative refractory period: K+ channels are open, Na+ channels closed.
• Action potential speed is affected by axon diameter (larger is faster) and myelination (increases conduction speed).
• Continuous conduction involves action potentials produced along the entire axon length.
• Saltatory conduction involves action potentials generated only at Nodes of Ranvier in myelinated axons, speeding up conduction.
• Action potentials occur only at Nodes of Ranvier in myelinated axons due to the presence of voltage-gated Na+ channels and the absence of myelination, which inhibits access to Na+ channels.
• The functional connection between a neuron and a neuron is a synapse, while between a neuron and muscle cell, it's a neuromuscular junction.
• Axodendritic synapses join axons to dendrites
  • Axoaxonic join axons to axons
  • Axosomatic join axons to soma
• A synapse conveys an action potential from a presynaptic neuron into a chemical signal, then converts it back to an ion current in the postsynaptic neuron via:
  • Action potential arrival: Voltage-gated Ca2+ channels open, and Ca2+ floods presynaptic cell synapse.
  • Synaptotagmin binds Ca2+: Promotes fusion of synaptic vesicles with axon membrane to cause neurotransmitter exocytosis into the synaptic cleft.
  • Neurotransmitter diffusion: Released neurotransmitter diffuses across the synaptic cleft and binds to the postsynaptic neuron receptors, causing chemically-gated ion channels to open.
  • Excitatory or inhibitory event: Depolarization or hyperpolarization of the membrane depending on which ions channels are affected
  • Depolarization: The membrane occurs and an action potential is then created in the post-synaptic cell
• Three mechanisms remove released neurotransmitters to terminate the synaptic signal: Re-uptake by astrocytes, degradation by enzymes, and diffusion away from the synaptic cleft.
• EPSP (excitatory postsynaptic potential) and IPSP (inhibitory postsynaptic potential) are graded potentials
  • EPSP: Involves opening Na+ or Ca+ channels, resulting in graded depolarization
  • IPSP: Involves the opening of K or Cl- channels resulting in graded hyperpolarization
• Neurotransmitters are endogenous chemicals transmitting signals from one neuron to its target cell across a synapse.

Neuroreceptors, Neurotransmitters, and the Central Nervous System

• Neuroreceptors (neurotransmitter receptors) are specific receptors to which neurotransmitters bind to elicit signaling.
• Neurotransmitter receptors are classified by how they transduce signals:
  • Ionotrophic receptors which are transmembrane ion channels that open/close in response to ligand binding
  • Metabotrophic receptors, which are G-protein coupled and separate from the proteins that serve as ion-channels.
• The 7 classes of neurotransmitters include: amines, acetylcholine, amino acids, purines, peptides, gases, and lipids.
• Acetylcholine receptors are either ionotrophic (nicotinic) or metabotrophic (muscarinic).
• The two subclasses of acetylcholine receptors are nicotinic (ionotrophic) and muscarinic (metabotrophic).
• Acetylcholineesterase is an enzyme that degrades acetylcholine into acetic acid and choline.
• Monoamine receptors are metabotrophic.
• Gamma-amino butyric acid (GABA) is a neurotransmitter widely used in the brain, involved in motor control, and inhibitory as it opens Cl- channels.
• The cerebrum is the largest part of the brain.
• The corpus callosum connects the left cerebral hemisphere with the right hemisphere.
• The 4 lobes of the cerebral cortex are frontal, temporal, parietal, and occipital.
• The precentral gyrus is anterior to the central sulcus and controls primary motor function
  • The postcentral gyrus is posterior to the central sulcus and functions for primary sensory somathestic senses.
• The temporal lobes are auditory centers
  • The occipital lobe is for vision and coordination of eye movement
  • The insula lobe encodes memory and integrates sensory information with visceral responses, receiving olfactory, gustatory, auditory, and pain information.
• Based on frequency (Hz), brain waves are classified into alpha, beta, theta, and delta.
• Theta brain waves are observed during REM sleep, while delta waves are seen during Non-REM sleep.
• Delta brain waves have the lowest frequency.
• Broca's area and Wernicke's area are the two areas in the brain controlling language.
• The angular gyrus integrates sensory information, involves language, math, cognition, and is responsible for understanding metaphors.
• The limbic system includes the thalamus, hypothalamus, cingulate gyrus, amygdala, hippocampus, septal nuclei, and anterior insula.

Limbic System, Diencephalon, and Spinal Cord

• The limbic system is responsible for memory, olfaction, autonomic control, neuroendocrine function, emotions, and drives ("MOANED").
• The fornix is a band of fibers that connects the hippocampus to the hypothalamus.
• Long-term memory is divided into declarative (explicit, verbalized) and non-declarative (implicit) categories.
• The diencephalon is formed by the epithalamus, hypothalamus, and thalamus.
• The brain stem is formed by the midbrain, pons, and medulla oblongata.
• The third ventricle is enclosed by the diencephalon.
• The thalamus is the largest structure of the diencephalon.
• The pineal gland secretes melatonin.
• The fourth ventricle separates the pons from the cerebellum.
• Respiratory and cardiovascular centers are located in the medulla oblongata.
• The reticular activating center, which forms part of the sleep-awake command center, includes the pons and reticular formation (a set of interconnected nuclei in the brain stem).
• Ascending tracts in the spinal cord are sensory neurons conveying information to the brain, involving three neurons in the neural pathway.
• There are four ascending tracts in the spinal cord: dorsal, spinothalamic, posterior spinocerebellar, and anterior spinocerebellar.
• There are twelve cranial nerves.
• There are thirty-one pairs of spinal nerves.
• The simplest reflex arc involves two neurons
  • A withdrawal reflex is more complex, involving three neurons.
• The five components of a reflex arc are: sensory receptor, sensory neurons, association neurons, motor neurons, and effectors.
• Autonomic control centers in the brain include the hypothalamus, pons, and medulla oblongata.
• The preganglionic neuron of the autonomic nervous system (ANS, visceral motor) originates in the CNS (midbrain, hindbrain, or thoracic, lumbar, or sacral region of the spinal cord).
• The postganglionic neuron of the ANS (visceral motor) originates in the autonomic ganglion.
• Somatic motor neurons are always stimulatory, while autonomic motor neurons can be either stimulatory or inhibitory.
• The two divisions of the ANS are the sympathetic and parasympathetic systems.
• Sympathetic preganglionic neurons arise from the thoracic and lumbar regions of the spinal cord.

Autonomic Nervous System

• The adrenal medulla is innervated by a type of neuron to secrete epinephrine/norepinephrine
  • It's a modified sympathetic ganglion where long preganglionic neurons project from the spinal cord and synapse with postganglionic neurons
  • These postganglionic neurons are chromaffin cells secreting epinephrine/norepinephrine directly into the blood
• Parasympathetic preganglionic neurons originate from the cranial and sacral regions of the CNS.
• Parasympathetic preganglionic fibers synapse with postganglionic fibers in the terminal or prevertebral ganglia, located close to or inside effector organs.
• Effectors in the skin and muscles (e.g., sweat glands, blood vessels, arrector pili) only receive sympathetic innervation.
• The oculomotor, facial, glossopharyngeal, and vagus nerves possess parasympathetic functions and contain parasympathetic preganglionic neurons.
• Parasympathetic postganglionic fibers are shorter than sympathetic postganglionic fibers.
• Sympathetic postganglionic fibers primarily release norepinephrine but can release acetylcholine, whereas parasympathetic postganglionic fibers release only acetylcholine.
• Both sympathetic and parasympathetic preganglionic fibers release acetylcholine.
• Cholinergic neurons use acetylcholine as the neurotransmitter, divided into nicotinic and muscarinic subclasses.
• Adrenergic neurons use norepinephrine as the neurotransmitter.
• Varicosities are the equivalent of synapses in the autonomic nervous system, similar to synapses in the somatic nervous system.
• All adrenergic receptors use G-proteins and second messenger systems.
• The heart's conducting system and ventricular musculature use β1 sympathetic adrenergic receptors.
• Acetylcholine (ACh) released from preganglionic neurons of both the sympathetic and parasympathetic divisions is always stimulatory.
• ACh from postganglionic neurons of the parasympathetic division can be stimulatory or inhibitory, depending on receptors.
• Nicotinic receptors are always stimulatory
  • Muscarinic receptors can be either stimulatory or inhibitory, depending on receptor subtypes
• Autonomic ganglia contain nicotinic neuroceptors
  • Effector organs contain muscarinic neuroceptors
• All nicotinic receptors are ion channels, whereas all muscarinic receptors are G-protein-coupled receptors.

Somatic and Special Senses

• The five somatic senses include touch, temperature, itch, pain, and proprioception.
• The five special senses are vision, hearing, taste, smell, and equilibrium.
• Proprioception, muscle tension, and stretch are somatic senses processed subconsciously.
• Interoceptors process internal stimuli, while exteroceptors process external stimuli.
• Phasic sensory receptors respond quickly and adapt rapidly, coding for stimulus intensity
• Tonic receptors adapt slowly, continuing to generate action potentials and coding for stimulus duration.
• Stimulus properties are coded by action potential frequency and duration.
• The Law of Specific Nerve Energies suggests that stimulus perception is directly related to the brain area where nerves end, not the stimulus itself.
• Graded potentials are depolarizations, that summated to reach a threshold to trigger an Action Potential
  • Action potential is generated by voltage-dependent Na channels and follows an all-or-none phenomenon
• Generator potentials are graded potentials from sensory receptors in response to a stimulus.
• Pain, heat, and cold are sensed by neurons with non-encapsulated free nerve endings.
• Meissner, Pacinian, and Ruffini corpuscles are examples of encapsulated sensory receptors.
• Somathetic senses are bodily feelings and include cutaneous senses (heat, cold, touch, pain), vestibular senses (equilibrium), and kinesthetic senses (muscle stretch and tension).
• The neural pathway for somathetic senses involves three neurons.
• Sensory neurons can decussate in the medulla oblongata (fine touch and proprioception) and spinal cord (pain, temperature, coarse touch).
• Chemoreceptors are used for taste and smell.
• Taste buds are receptors for tastes.
• Fungiform, foliate, and circumvallate are the three types of lingual papillae that contain taste buds.
• Gustatory sensory information is conveyed to the brain by the facial, glossopharyngeal, and vagus cranial nerves.

Taste, Smell, Equillibrium and Hearing

• The five taste categories are: sweet (sugar), umami (glutamate), salty (Na+), sour (H+), and bitter (quinine).
• Sweet, umami, and bitter taste sensations use G-proteins called gustducins.
• The olfactory epithelium uses a signaling system with G-proteins, adenylate cyclase-cAMP, which opens Na+ and Ca+ channels.
• Semicircular canals and otolith organs (saccule and utricle) are the organs responsible for equilibrium.
• Maculae and crista ampullaris is the name for the receptor organs in the otoliths and semicircular canals.
• Hair cells are the sensory receptor cells for hearing, located in the organ of Corti.
• The utricle and saccule in the inner ear provide sensory information on linear acceleration.
• Saccule is responsible for vertical movements
  • Utricle, for horizontal and lateral movements
• Crista ampullaris is the sensory organ for rotational equilibrium.
• Endolymph is the inner ear fluid within the semicircular canals.
• The cochlea of the inner ear has three chambers:
  • Scala vestibule (perilymph)
  • Scala media (endolymph)
  • Scala tympani (perilymph)
• The basilar membrane in the scala media vibrates according to different sound frequencies.
• The neural pathway for hearing:
  • Vestibulocochlear nerve to Medulla oblongata to Inferior colliculus of midbrain to Thalamus to Auditory cortex of temporal lobe.

Eyes

• Light enters the eye through the cornea, aqueous humor, lens, vitreous humor, and entire neural layer of the retina to photoreceptors.
• Light is refracted three times when entering the eye: at the entering cornea, entering lens, and exiting lens.
• Parasympathetic stimulation constricts the circular muscles of the iris, causing pupil constriction.
• Sympathetic stimulation contracts the radial muscles of the iris, causing pupil dilation.
• Sympathetic input relaxes the ciliary muscle, tightening the ciliary zonule and flattening the lens for distant vision.
• To clearly see light from close objects, simultaneous adjustments must be made: accommodation of lenses, constriction of pupils, and convergence of eyeballs.
• Parasympathetic input contracts the ciliary muscle, loosening the ciliary zonule, allowing the lens to bulge for close vision.
• The neural layer of the retina has three types of neurons: photoreceptor cells (rods and cones), bipolar cells, and ganglion cells.
• Light travels to the retina in this order: ganglion to bipolar to photoreceptor.
• The nerve signals go directly to the optic nerve> from the ganglion cells

Endocrine Glands and Hormones

• The five pure endocrine glands are: pituitary, pineal, thyroid, parathyroids, and adrenals.
• The two neuroendocrine glands are the hypothalamus and adrenals.
• The Islets of Langerhans produce insulin and glucagon.
• Endocrine glands regulate hormone secretion through negative feedback inhibition.
• Differences between the Nervous System and Endocrine System in communication:
  • Endocrine uses hormones, is usually slow and longer lasting, and broadcasts through the blood stream
    • Nervous uses electrochemical mediators, is usually fast-responding and short lasting, and exerts point-to-point control through nerves.
• Target cells in endocrine physiology are cells able to respond to a hormone due to specific receptors.
• The four types of hormone actions:
  • Endocrine: hormones are distributed in blood and act on distant target cells
  • Autocrine: hormones act on the same cell that produces them
  • Paracrine: hormones act on nearby target cells
  • Intracrine: hormones acting inside the cell
• The posterior pituitary secretes ADH and Oxytocin.
• The anterior pituitary secretes FLAT-PEG (FSH, LH, ACTH, TSH, PRL, GH).
• FSH, LH, TSH, and ACTH are trophic hormones.
• Hormones are classified into amines, peptides and proteins, steroids, and lipids/fatty acids.
• Water-soluble polar hormones use cell surface membrane receptors.
• Lipid-soluble nonpolar hormones use intracellular receptors.
• Peptide and protein hormones and amines (except thyroid hormones) must be injected to be effective.
• Thyroid hormones are the amine-based hormones that are not water-soluble.
• Prehormones are precursor forms that must be processed into active mature hormones.
• Hormone concentrations in the bloodstream are affected by production rate, delivery rate, and degradation/elimination rate.
• Hormone interactions can be permissive, antagonistic, and synergistic.
• Hormone binding to target cells shows high specificity, high affinity, and low capacity.
• Steroid hormones diffuse across the cell membrane, bind to intracellular receptors to initiate protein creation
• Up-regulation is where target cells form more receptors in response to low hormone levels
• Down-regulation is where target cells lose receptors in response to high hormone levels
• Pulsatile secretion involves episodic hormone release, causing hormone levels to rise and fall in a regular rhythmic pattern.
• Hormones are released by endocrine cells in response to humoral, hormonal, and neural stimuli.
• Trophic hormones stimulate another endocrine organ to secrete hormones.
• ADH and oxytocin are synthesized in the paraventricular and supraoptic nuclei of the hypothalamus, then transported to the posterior pituitary
• ADH deficiency causes Diabetes Insipidus.
• The hypophyseal portal system connects the hypothalamus to the anterior pituitary
  • Is comprised of primary capillary plexus, hypophyseal portal veins and secondary capillary plexus.
• Hypophyseal portal veins connect the primary capillary plexus to the secondary capillary plexus.
• Releasing and inhibiting hormones hormones are carried by the hypophyseal portal veins.
• Six hypothalamic hormones. CRH, GRH, PIH, GRIH, TRH and GHRH
• Somatotropes cells are in the Anterior pituitary produce GH
  • Gonadotropes LH and FSH
  • Lactotropes PRL
  • Corticotropes ACTH
  • Thyrotropes TSH
• The function of corticotrophin ACTH>
  • Stimulates Adrenal cortex to produce Corticosteroids
• What hypothalamic hormone trigger the release of ACTH from the pituitary?
  • CRH corticotropin releasing hormones
• What hypothalamic hormones trigger the release of LH and FSH from the pituitary? - GnRH gonadotropin releasing hormones
• What are actions of FSH and LH?
  • FSH stimulates Gemete production
  • LH Stimulates sex hormone reproduction

Adrenal and Thyroid Hormones , and Glucose Hormones

• The adrenal cortex has three layers that produce particular corticosteroids
  • Zona glomerulosa (mineralocorticoids like aldosterone),Zona fasciculate (glucocorticoids like cortisol), Zona reticularis (gonadocorticoids such as DHEA)
• Aldosterone stimulates Na+ reabsorption and water retention, plus K+ elimination in kidneys.
• Cortisol keeps blood glucose levels constant and maintains blood pressure, increasing action of vasoconstrictors
• Hypersecretion- Cushing and hyposecretion causes Addison diseases
• Chromaffin cells produce epinephrine and norepinephrine in the adrenal medulla.
• Thyroid glands produce thyroid hormones and calcitonin.
• Follicular cells produce thyroid hormones
  • Parafollicular cells produce calcitonin
• Thyroid hormone (TH) major metabolic hormone and heat production stimulates developments of the nervous and reproductive system
• Parathyroid glands secrete parathyroid hormone, which controls Ca2+ in the blood
• Pancreas dual endocrine-exocrine
• Acinar cells of the pancreas produces pancreatic digestive enzymes Islets of Langerhans are Alpha cells glugacon Beta cells- Insulin
  • Liver-Major target glucagon
• Stimulates glycogenolysis and glucogeogenesis
• Target tissues for nsulin- Adipose and muscles
• insulinStimulates glucose uptake by target tissues, and inhibits glycogenolysis and gluconeogenesis
• Glucose transporters are affected by insulin- GLUT4
• Three signs of diabetes mellitus: Polydipsia increased thirst polyuria Increase urine output and polyphagia increased appetite
• Ovaries produces Estogen and progesterone hormones
• Placenta produces Estrogen progesterone HCG hormones
• Estrogen progesterone HCG hormones Testos produces Testosterone