Midterm Review (Lecture 6, 7)

neuropharmacology and Sensory transduction

Neuropharmacology

the scientific study of how drugs, medications, and chemicals affect the cellular and molecular functions of the nervous system.

what are the 2 major types of NTs?

• small molecule NTs (classical NTs) — modified amino acides (except for acetylcholine, which is synthesized from a b-vitamine nutrient called choline)

• neuropeptides (which often function as hormones to send signals over long distances) are small protein molecules (sequences of several amino acids)

proteins

chained molecules formed by animo acids

glutamate synthesis

• glutamate is the dominant excitatory NT in the brain, so it is synthesized in many, many neurons

• an enzyme called glutamate synthase converts glutamine into glutamate

GABA synthesis

• Gamma-amino-butyric acid (GABA) is the dominant inhibitory NT in the CNS

• an enzyme called glutamate decarboxylase (GAD) converts glutamate into GABA

why does glu excite while GABA inhibits?

• because they bind to different postSYN receptors

• the response of the postSYN neuron is determined by the properties of the postSYN receptor, NOT by the properties of the preSYN NT molecule

• when NT molecules bind to a neurons receptors, those receptors cause some physiological or chemical reponse in the neuron

2 major categories of receptors

1. ionotropic receptors (ligand-gated ion channels) - opened by NT binding, to make the membrane more permeable to cations (Na+, K+, Ca++) or anions (Cl-)

2. metabotropic receptors (G-protein coupled receptors) — that are activated when NT binds to the extra-cellular domain of the receptor protein, thereby causing a linked G-protein to be released from the intracellular domain of teh receptor protein, and then float through the cytoplasm until it binds to various targets

   1. a g-protein can attach to many other targets that activate various cellular signaling pathways

what is a G-protein coupled receptor?

how does the GPCRs work?

the largest family of cell-surface receptors in the human body, acting as cellular "inboxes". They detect external chemical and physical signals—like hormones, neurotransmitters, and light—and translate them into internal cellular actions, making them the target for roughly 30% of all modern medicines

ligand

a signaling molecule that is bound to a receiving molecule (the receptor)
* come in closely matched pairs, with a receptor recognizing just one (or a few) specific ligands, and a ligand binding to just one (or a few) target receptors

• binding of a lignad to a receptor changes its shape or activity, allowing it to transmit a signal or directly produce a change inside of the cell

endogenous vs exogenous ligands

• endogenous ligands of a receptor are chemicals normally found in the body which bind to the receptor

• exogenous ligands of a receptor are compounds not found in the body that, when introduced into the body, can affect the receptor in 1 of 2 ways:

  • agonist - binds to the recpetor and activate it in mushc the same way as its normal endogenous ligands

  • antagonist - binds to the receptor and prevent it from being activated by its normal ligand

• many drugs that affect our nervous systems are exogenous ligands for NTs

antagonist drugs work in 2 ways

• competitive binding - teh drug attaches to the receptor and blocks the normal ligand binding site

• noncompetitive binding - the durg attaches to the receptor and prevents it frombeing activated, no blocking the normal ligand bindign site

  • endogenous ligand can still bind to recpetor, but no activation

what are modulatory NTs?

what are catecholamines?

• hormones and NTs produced by the brain, nerve tissues, and adrenal glands

• pimary ones — dopamine, norepinephrine/noradrenaline, and epinephrine / adrenaline

• synthesized from the animo acid (tyrosine)

1. tyrosine is catalyzed into DOPA by tyrosine hydroxylase, and DOPA is then converted into dopamine by L-amino acid decarboxylase

2. NE is synthesized from dopamine by Dopamine β-hydroxylase

3. E is synthesized from NE by phenylethanolamine-N-methyltransferase

adenylate / adenylyl cyclase

ACs are a family of enzymatic proteins. Most of them attach to the intracellular side of the cell membrane

• AC enzymes catalyze the conversion of (ATP) adenosine triphosphate into cyclic AMP (cAMP- adenosine monophosphate) and pyrophosphate (PP)

  • cyclic - ring shape of cAMP

• a major action of cAMP is to regulate cAMP-dependent kinases such as protein kinase A (PKA)

catalyzed

something that has been accelerated or sparked by a catalyst. In science, it refers to a chemical reaction sped up by a substance that remains unchanged.

• catalyst = anything that speeds up or triggers a major change without being affected or consumed in the process.

• In chemistry, a catalyst is a substance that speeds up a chemical reaction (or lowers the energy needed to start it) without being permanently changed or used up itself.

what are the different types of somatosensation (body sensation)?

• disciminative touch

• proprioception — positon of joints and limbs

• nociception — pain and temperature (tissue damage, heat, cold)

dermatomes

the area of skin innervated by a single spinal nerve

• innervated - a body part, tissue, organ being supplied with nerves (distribution of nerve fibers that carry signals between that area and the nervous system, allowing for motor control (movement) and sensory feedback)

spinal cord segments (5 groups of somatosensory dermatoses/ areas)

1. cervical (C1-C8) - arms and back of head

2. thoracic (T1-T12) - back and stomach

3. lumbar (L1-L5) - lower back and front of legs

4. sacral (S1-S5) - buttocks and back of legs

5. coccygeal (1) - pelvis and groin

unilateral / bilateral

• unilateral - one side

• / bilateral - two sides

ipsilateral / contralateral

• ipsi = same side of the body

• contra- = opposite side of the body

dorsal

back, anterior, upper

ventral

front, belly, lower side of body / anterior

rostral

towards the beak or nose
*

• upper cranial, superior,

caudal

towards the tail, the hind part of the bdoy , further away from the head

transduction

the conversion of energy from one form into another

• all sensory systems transduce some form of energy into APs (nerve signals)

• vision: photoreceptors convert light energy to nerve singals

• hearing: mechanoreceptors convert sound waves (energy) into nerve signals

• touch: mechanoreceptors sense pressure, thermoreceptors sense temp, chemoreceptors sense tissue damage

• smell and taste: chemoreceptors sense odorants and tastants

• other; homeostatic sensors for blood pressure, hydration, tiredness, etc.

Generator (receptor) potentials

the opening of the mechanically gated Na channels (stretch sensitive) causes excitatory potentials (similar to EPSPs) and thereby transduces mechanical energy into electrical energy

• a weak touch stimulus causes a weak (subthreshold) generator P,

• a strong touch stimulus —> can trigger APs in the receptor neuron (DRG cell)

what is the preferred stimuli of discriminative touch?

different kinds of receptors in the skin sense different kinds of discrinative touch stimuli by transducing different kinds of energy

corpus callosum

a major comissure that connects the left and right cerebral hemispheres in the brain

anterior white commissure

in the spinal cord = where the dorsal horn interneurons that are exicted by A S and C fibers cross the midline

commissures

axon bundles that carry info from one side of the brian or spinal cord to the opposite side

decussations

midline crossings

center-surround receptive fields

each neuron in the somatosensory cortex responds to a patch of skin with an excitatory center and inhibitory surround

Acetylcholine (Ach)

synthesized by combineing choline (one of the b vitamins) with acetate (acetyl-CoA); this is done by choline acetyltransferase

• Ach is released by neurons with cell bodies in the basal forebrain (nucleus basalis + medial septum) that send axons all over the brain

basal forebrain

a cluster of structures located near the bottom of the front of the brain

• It is primarily responsible for regulating arousal, attention, and memory through the widespread release of acetylcholine. Its dysfunction is closely linked to cognitive decline and Alzheimer's disease

  

Ach Receptors

Nicotinic receptors and muscarinic receptors

Nicotinic receptors

• ligand-gated cation channels iwth a 5-subunit strcurure similar to GABA-A channels

• in teh PNS, Ach is the excitatory NT released by motor neurons to activate muscle fibers at the neuromsucular junction (exclusively via nictonic receptors)

• nicotinic agonists = Nicotine

• Nicotinic antagonists =

  • curare (paralytic arrow poison)

  • various muscle relaxants

Muscarinic Ach Receptors

• there are 5 major subtypes of MR, distributed throughout the CNS and PNS

• Muscarinic agonists = muscarine - a nerve toxin found in some speciries of poisonous mushrooms

• muscarinic antagonists =

  • atropine = surgical anesthesia to treat bradycardia (slow heart rate)

  • scopalamine = low doses to treat motion sickness, higher doeses causes amnesia

Endocannabinoids

neuromodulatory lipids

• a major exogenous ligand for cannabinoid receptors