Actual Neurosys Review 1 PDF

24 QUESTIONS- 10 MC; 3 bonus questions, then definition/ really short short answers, then short answer Somatic vs Behavioral interventions - Somatic interventions: manipulating the body or brain to observe changes in behavior - Behavioral interventions: altering behavior or environmental fact...

24 QUESTIONS- 10 MC; 3 bonus questions, then definition/ really short short answers, then short answer Somatic vs Behavioral interventions - Somatic interventions: manipulating the body or brain to observe changes in behavior - Behavioral interventions: altering behavior or environmental factors to observe changes in the body or brain Anatomy of the neuron 1. Parts of the neuron 2. Types of dendritic spines Membrane & Action potential - Role of Voltage gated Na+ channels - Role of Voltage gated K+ channels - Role of Na+- K+ ATP pump - Role of delayed rectifier K+ channels - Nernst Equation- You will not have to perform calculations, but you will need to understand how changing ionic concentrations on the inside and outside of the cell impacts the equilibrium potential - Impact of selective permeability on the membrane potential - Selective permeability of the cell membrane maintains membrane potential by allowing differential movement of ions, particularly sodium and potassium, which creates an electrochemical gradient. - Conductances: How does changing the conductance of Na+ and K+ impact the AP? - Higher conductance Na+ faster depolarizing for AP - Higher conductance K+ faster repolarizing to get back to resting - Ion channel kinetics (timing of channel openings) and how do each of these influence the AP? How would alterations of these impact communication between neurons? 1. Activation (Opening of channels) → Pace of depolarization or repolarization phase a. Faster activation: could lead to faster signal transmission. 2. Deactivation (Closing of channels) → Impacts the duration and shape of AP (repolarization) a. Slower deactivation: might prolong the action potential duration, leading to prolonged signaling or altered synaptic plasticity. 3. Inactivation (Inactivation gate within the Na +channel) → Important for repolarization and the refractory period  a. Impaired inactivation: of Na+ channels can cause prolonged depolarization, resulting in repetitive firing Neuronal shapes and sizes - How would you classify a neuron if you were viewing it through a microscope? - Number of extensions from cell body, shape of the tree, cell body - What is an interneuron? What is its role in the Patellar (knee) reflex? - An interneuron is a type of neuron that connects sensory and motor neurons within the central nervous system, and in the patellar reflex, it helps coordinate the reflex arc by relaying signals between these neurons. - Excitation → excitation for quads - Excitation actives inhibition neurons for hamstrings - Motor information coming out of root – excitation of quads muscles, inhibition of hamstring muscles Conditioning: which brain regions are involved? 1. Classical- 2. Operant- Visualizing the brain 1. Nissl stain vs golgi stain a. Nissl stain: highlights cell bodies and rough endoplasmic ER by staining RNA b. Golgi Stain: selectively labels entire neurons, including dendrites and axons —> reveals full cellular morphology 2. MRI vs PET a. PET: radioactive injection to trace metabolic activity b. fMRI: understands changes in blood flow, images activated brain areas 3. Tract tracing when would this technique be useful? What kind of information could you gather from it? GPCR signaling 1. Gs vs Gi vs Gq Gq: modulatory Gi: inhibitory Gs: stimulatory 2. Secondary messengers (metabotropic)→ open up ion channels from inside of cell ▪ cAMP (created from ATP by adenylyl cyclase) ▪ IP3 & DAG (created from PIP3 by phospholipase C) Commissural vs association fibers - Where do they arise from in the cerebral cortex Commissural fibers: connect corresponding areas between the two opposite hemispheres of the cerebral cortex, primarily arising from the corpus callosum, balance excitation and inhibition (same sides talking to each other) Association fibers: connect different regions within the same hemisphere, arising from various cortical regions. (different regions talking to each other) Basal Ganglia: Body's voluntary movements Substantia Nigra: Production of dopamine Caudate Nucleus: Planning movement (& other high-level functions)  Putamen: Contains parallel circuits allowing for cortico-subcortical-cortical loops. Inhibitory projections to the thalamus (GABAergic) Excitatory projections from the thalamus (Dopaminergic) Globus Pallidus: Regulation of voluntary movement Internus → Outputs (GABA) Externus → Inputs (GABA) Subthalamic nucleus Projects Glutamatergic neurons to the globus pallidus internus ▪ NTs used in each projection Limbic System: Series of structures important for emotion, learning, and memory Cingulate gyrus: Regulation of emotion & pain Hippocampus: Learning & Memory Fornix: Output tract for the hippocampus Amygdala: Regulation of fear/emotional cues Stria terminalis: Efferent fibers from the amygdala Septal Nuclei: Collection of cell bodies which regulate the rhythm of the hippocampus ▪ NTs used in each projection Frontostriatal circuit o Function emotion , cognition, motor; executive function/decision making, motor regulation, reward/motivation, emotional regulation o Structures Inferior frontal junction: associated w integrating stimulus, maintenance during a task Caudate nucleus: DA synthesis, cognitive processes (ie: high level thinking) Thalamus: sensory/relay station; integrating senses; supports PFC neurons during working memory delay periods o NTs used DA, Glu, GABA Postsynaptic Potentials from across the cell body summate at the axon hillock → determines if AP is fired Temporal summation: PSP’s that reach the axon hillock at different times → harder to teach threshold the further they are apart Occurs when multiple postsynaptic potentials (PSPs) arrive at the axon hillock in quick succession. The closer these potentials are in time, the more they can sum up to trigger an action potential. If too much time passes between EPSPs (excitatory postsynaptic potentials), they will fade before the next arrives, preventing the neuron from firing. Spatial summation: PSP that reach the axon hillock at the same time → AP is triggered when summation reaches threshold Refers to the summation of PSPs that come from different physical locations on the neuron. If the total summation reaches the threshold, an action potential is triggered. This process integrates inputs from multiple presynaptic neurons to fire a signal. Steps of NT release at the axon terminal  1. Action potential reaches at the axon terminal. 2. Depolarization opens voltage-gated Ca 2+ channels, allowing (Ca2+) to enter. 3. Ca2+ triggers synaptic vesicles to fuse with the presynaptic membrane and release NT molecules into the synaptic cleft. 4. NT cross the cleft and bind to receptors on the postsynaptic membrane. 5. This creates either an EPSP or IPSP in the postsynaptic neuron. 6. The neurotransmitter is then inactivated either by enzyme degradation or removed by reuptake transporters. Determining Factor: more AP —> more Ca 2+ —> more release Kiss and Run: 1 AP Partial Release: Bunch of AP Full Release: Bunch of AP Types of synapses and their function o Axo-dendritic: Refers to a synapse where the presynaptic axon terminal connects to a dendrite of the postsynaptic neuron, typically to influence signal reception. o Axo-somatic: The presynaptic axon terminal synapses directly onto the soma (cell body) of the postsynaptic neuron, often exerting a stronger influence on neuron firing due to proximity to the axon hillock. o Axo-axonic: A synapse where one axon terminal synapses onto another axon terminal, usually regulating the amount of neurotransmitter released by the target terminal o Dendro-dendritic: A synapse between the dendrites of two neurons, allowing coordination of activities between those neurons. Chemogenetics o DREADD (designer receptor exclusively activated by designer drugs) ▪ What is a DREADD receptor? What types are there? A DREADD receptor is a synthetic G-protein coupled receptor → unresponsive to natural ligands and only respond to synthetic ligands (drugs) hM4Di: Inhibitory DREADD is coupled to the Gi protein, resulting in decreased neuronal activity when activated. hM3Dq: Excitatory DREADD is coupled to the Gq protein, causing increased neuronal activity when activated. ▪ What compound is used to activate it? Clozapine-N-oxide (CNO) is the synthetic ligand that was used to activate both receptors, ▪ How can it be used to investigate functional networks of the brain?  ▪ How was it used to understand the acute effects of ketamine on depression? Ketamine cannot have its own antidepressant effect Optogenetics 1. Channelrhodopsin: An ion channel protein that when stimulated by light depolarizes neurons. a. Sensitive to blue wavelengths ; opens Na+ channels -> depolarizes the cell -> reads to an excitatory response 2. Halorhodopsin: An ion channel protein that when stimulated by light hyperpolarizes the neurons. a. Sensitive to yellow wavelengths ; opens Cl-channels -> hyperpolarizes the cell -> leads to an inhibitory response 3. How are these different from DREADD receptors? Glutamatergic signaling an opening of Na+ channels 1. AMPAR: Ionotropic glutamate receptors → Glutamate binds to Rapid influx of Na+ ions → Fast excitatory postsynaptic potential (EPSP). a. The EPSP's speed and amplitude determine the neuron's firing. 2. NMDAR: Ionotropic → Na+ influx is voltage-dependent 3. mGluR: Metabotropic GPCR → Don't directly open Na+ channels → Slow reaction GABAergic signaling o GABAA vs GABAB vs GABAC GABAA ○ ionotropic receptors that function as ligand-gated chloride channels. ○ When GABA binds to GABAA, it opens the chloride channels, allowing chloride ions to enter the neuron, causing hyperpolarization (inhibition). ○ Mediate fast synaptic inhibition. GABAB ○ metabotropic receptors that work through G-protein-coupled mechanisms. ○ Activation of GABAB receptors leads to the opening of potassium channels and inhibition of calcium channels, causing hyperpolarization and reducing neurotransmitter release. ○ Mediate slow and prolonged inhibitory signaling, and are often involved in presynaptic inhibition. GABAC ○ These are ionotropic receptors similar to GABAA​, but they have a different subunit composition and are less widely distributed in the CNS. ○ GABAC receptors are found primarily in the retina and mediate inhibitory signaling there. ○ Unlike GABAA, GABAC​receptors are insensitive to benzodiazepines. ○ chloride channels ▪ Which type of GABA receptor do benzodiazepines and alcohol work on?  GABAA Benzodiazepines act by increasing the frequency of chloride channel opening, making neurons less likely to fire. - Acetylcholine o Where is it produced? Basal forebrain, pedunculopontine nucleus, and laterodorsal tegmental nucleus. o Which enzyme is responsible for its production? Choline acetyltransferase o Which enzyme is responsible for its breakdown? Acetylcholinesterase - Dopamine o Where is it produced? Dopaminergic neurons in the ventral tegmental area and substantia nigra o Which enzyme is responsible for its production? Tyrosine hydroxylase and aromatic L-amino acid decarboxylase o What is the difference between D1-like and D2-like receptors? D1: Stimulates neuronal activity; activates adenylate cyclase, which increases the production of cyclic AMP (cAMP). D2: Inhibit neuronal activity; inhibits adenylate cyclase, reducing cAMP levels - Serotonin o Where is it produced? Raphe nuclei o Which enzyme is responsible for its production? Tryptophan hydroxylase and aromatic L-amino acid decarboxylase o What is the difference between 5-HT1 and 5-HT2? Which receptor does MDMA act on? 5-HT1: Act through Gi/Go proteins, which inhibit adenylate cyclase and decrease cAMP levels in the neuron, reducing excitability. 5-HT2 : Work through Gq proteins, which activate phospholipase C, increasing inositol trisphosphate (IP3) and diacylglycerol (DAG), leading to the release of intracellular calcium. MDMA enhances serotonin activity by increasing its release; act on 5-HT2A receptors. - Norepinephrine o Where is it produced? Locus coeruleus and lateral tegmental area o Which enzyme is responsible for its production? Dopamine beta-hydroxylase o What is the difference between norepinephrine and epinephrine? Norepinephrine is NT; released from sympathetic nerve terminals and influences target organs by stimulating adrenergic receptors; greater affinity for alpha-adrenergic receptors than beta-adrenergic receptors Epinephrine is hormone; secreted by the adrenal medulla during the "fight or flight" response; affects both alpha-adrenergic and beta-adrenergic receptors DIFFERENT AFFINITY - Definitions of agonist, antagonist, and inverse agonist agonist activates a receptor to produce a biological response an antagonist blocks the receptor to prevent activation an inverse agonist binds to the same receptor but induces the opposite effect of an agonist. Dose response curves o Effective dose vs lethal dose ▪ What does the difference between these two represent?  The difference between the effective dose (ED) and the lethal dose (LD) represents the therapeutic index, indicating the safety margin of a drug, where a wider gap signifies a safer drug with a lower risk of causing harm at therapeutic levels. Tolerance o What is the difference between functional and metabolic tolerance? a. Metabolic tolerance- occurs when body becomes increasingly effective at eliminating the drug i. Metabolizing or secreting whatever is the drug ii. Ie: alcohol iii. Increases activity of certain enzymes b. Functional tolerance occurs when the receptors become less sensitive to the drug i. Downregulation & upregulation. ii. Modulating number of receptors iii. AGONIST WILL ACTIVE RECEPTOR iv. TOO MUCH OF AN AGONIST BODY WILL SAY IM GONNA LOWER VOLUME AND SO BODY HAS LESS RECEPTORS 1. IE: COCAINE AND METH v. ANTAGONIST→ BODY WILL RESPOND FUNCTIONALLY BY INCREASING NUMBER OF RECEPTORS AND WILL INCREASE RECEPTORS IN RECEIVING ZONE What types of responses would you expect to see from the cell in response to an agonist vs an antagonist drug? ○ In response to an agonist drug, the cell would exhibit activation and initiate a biological response ○ response to an antagonist drug, the cell would show inhibition, preventing the receptor from being activated and producing any effect. Presynaptic drug effects a how would this impact the postsynaptic response? Transmitter production Transmitter release Transmitter clearance Postsynaptic drug effects a how would this impact the postsynaptic response? ○ Blockade of receptors ○ Activation of receptors ○ Regulation of receptor expression ○ Modulation of intracellular signals (i.e. blocking GPCR activation) CLASS REVIEW - Inhibition is an active process - Manville - Kv2.1 is known as a delayed rectifier Kv channel - Regulates the duration and resting membrane potential of action potential in certain cells - Q: if this process takes longer → what does this do to the cells firing AP - A: make it harder; makes release of NE harder; would expect to see learning deficits, alert deficits, alterations in sleep/wake cycle - Therefore, regulating of firing of AP is really important - S114R slows kv2.1 inactivation - Recovery from inactivation which reflects refractory period by using a double pulse protocol - Ions still passing through → just takes longer to reach resting (what specific mutation was doing) - Rawat - From class review - Q: what is determining whether we have Kiss and Run, partial release, or full release - A: If you have 1 action potential —> kiss and run - THE MORE ACTION POTENTIALS THE MORE CALCIUM THE MORE NT RELEASE - Q: what is necessary in order to release NT into synaptic cleft - A: amount of time for fuse (entering Ca2+ binds to synaptotagmin) - Q: what is the difference between an association fiver and commissural fiber - A: primary visual, primary auditory, secondary visual, secondary auditory - Association - Raw data and associated it with significance - Multiple function to multiple regions of brain in order to form more complex - Commisoral - Regions of the brain have to connect with one another or be associate with one another