NRS 250 Final - ALL

Sensory System General Principles 

• Sensory cells and receptors 

• Specialized cells (photoreceptors, mechanoreceptors, etc.) detect specific environmental stimuli. 

• They initiate sensory transduction by converting stimuli into neural signals. 

• Transduction pathway 

• Stimulus → Transduction at sensory receptor → Receptor potential (graded) → Encoding → Action potential generation. 

• Receptor potentials are passive signals, like postsynaptic potentials. 

• Receptive field 

• A neuron's receptive field is the region where stimulus evokes a response. 

• Smaller fields = finer spatial resolution (e.g., lips vs. back). 

• Lateral inhibition 

• Enhances contrast at edges by having neurons inhibit neighbors with overlapping receptive fields. 

• Common in visual and tactile systems. 

Neural Coding 

• Type of stimulus 

• Labeled line coding: Each neuron type is dedicated to one modality (e.g., pain receptors only signal pain). 

• Population coding: A stimulus is represented by the pattern of activity across multiple neurons (e.g., color vision). 

• Stimulus intensity 

• Labeled lines: Stronger stimulus recruits more fibers. 

• Frequency coding: Stronger stimulus = higher firing rate. 

Visual System 

• Light 

• Electromagnetic wave detected by photoreceptors. 

• Retina 

• Layers: photoreceptors → bipolar cells → ganglion cells. 

• Distribution: cones densely packed in the fovea; rods more common in the periphery. 

• Phototransduction 

• Light causes photoreceptor hyperpolarization, reducing glutamate release. 

• On-center bipolar cells depolarize when light hits center; off-center do the opposite. 

• Central pathway 

• Retina → Optic nerve → Optic chiasm → LGN (thalamus) → Primary visual cortex (V1). 

• V1 is organized retinotopically, with columns for orientation and eye dominance. 

• Streams 

• Dorsal (“where”): spatial location and motion. 

• Ventral (“what”): object identity and color. 

Auditory System 

• Sound 

• Vibrations of air molecules; frequency = pitch, amplitude = loudness. 

• Transmission 

• Outer ear → Tympanic membrane → Ossicles → Oval window → Cochlea. 

• Cochlea 

• Contains Organ of Corti with hair cells on basilar membrane. 

• Frequency discrimination via tonotopic map: base = high freq, apex = low freq. 

• Cochlear implants directly stimulate auditory nerve. 

• Central processing 

• Auditory nerve → Cochlear nucleus → Superior olive → Inferior colliculus → MGN → Auditory cortex. 

• Sound localization 

• Horizontal: time and intensity differences via superior olive. 

• Vertical: shape of the pinna alters sound. 

Gustatory System 

• Five tastes & transduction 

• Salty & Sour: ionotropic (Na+, H+). 

• Sweet, Bitter, Umami: G-protein coupled receptors (metabotropic). 

• Taste encoding 

• Labeled lines and population coding. 

• Brain interprets pattern across taste neurons. 

Olfactory System 

• Nasal epithelium 

• Olfactory receptor neurons have cilia with odorant receptors. 

• Transduction 

• Odorant binds receptor → G-protein Golf → ↑cAMP → opens Na+/Ca²⁺ channels → depolarization → APs. 

• Population coding 

• Odors activate multiple receptor types in unique combinations. 

• Central processing 

• Olfactory nerve → Olfactory bulb → Olfactory cortex. 

• Bypasses the thalamus, unique among sensory systems. 

The Spinal Cord: Structures 

• The spinal cord is a long, thin structure of nervous tissue running from the brainstem to the lower back. 

• It is housed within the vertebral column and divided into four regions: cervical, thoracic, lumbar, sacral. 

• Each segment gives rise to afferent (sensory) and efferent (motor) roots. 

• Dorsal roots carry sensory input; ventral roots carry motor output. 

Autonomic Nervous System (ANS) 

• Composed of a two-neuron chain: a preganglionic neuron and a postganglionic neuron. 

• Preganglionic neurons release acetylcholine (ACh) onto nicotinic receptors in ganglia. 

• Postganglionic neurons release ACh or norepinephrine, depending on receptor type. 

Sympathetic vs Parasympathetic Divisions 

• Sympathetic (fight-or-flight): short preganglionic, long postganglionic neurons; release norepinephrine. 

• Parasympathetic (rest-and-digest): long preganglionic, short postganglionic neurons; release ACh. 

• Dual innervation of organs allows coordinated responses. 

The Motor Unit 

• A motor unit = one alpha motor neuron + all the muscle fibers it innervates. 

• Motor pools = all motor neurons innervating one muscle. 

Muscle Spindle & Myotatic Reflex 

• Muscle spindle detects stretch; contains intrafusal fibers. 

• Stretch activates Ia afferents, causing reflexive muscle contraction (e.g., knee-jerk). 

• Circuit: Ia sensory → alpha motor neuron → same muscle; inhibitory interneuron → antagonistic muscle. 

Withdrawal & Crossed Extension Reflex 

• Withdrawal: quickly pulls a limb from a painful stimulus. 

• Crossed extension: extends the opposite limb to support body weight during withdrawal. 

γ Motor Neurons 

• Innervate intrafusal fibers in muscle spindles. 

• γ co-activation ensures spindle sensitivity during movement. 

• γ loop: stretch → Ia afferent → α motor neuron → contraction → intrafusal adjustment via γ activation. 

Spinal Reflexes & Central Pattern Generators (CPGs) 

• CPGs = spinal networks generating rhythmic patterns like walking, independent of brain input. 

• In quadrupeds, CPGs coordinate alternating gait across limbs. 

Planning Movement 

• Premotor cortex: involved in preparing movement. 

• Prefrontal cortex: involved in intention and decision-making. 

• Monkey experiment: light panels showed premotor activation before movement. 

• fMRI study: imagined movement activated motor planning areas. 

• Mirror neurons: fire when observing or performing actions. 

Executing Movement 

• Primary motor cortex (M1): located in precentral gyrus; initiates voluntary movement. 

• Uses population coding: groups of neurons encode direction/intensity of movement. 

• Corticospinal tract: major descending motor pathway controlling distal muscles. 

Basal Ganglia Components

Includes: Striatum (caudate + putamen), Globus pallidus, Substantia nigra, Subthalamic nucleus. 

Basal Ganglia Pathways

• Direct pathway: facilitates movement via disinhibition of thalamus. 

• Indirect pathway: inhibits movement by enhancing thalamic inhibition. 

• Purpose: focused selection of motor programs, filtering inappropriate ones. 

Parkinson’s Symptoms

Bradykinesia, tremor, rigidity, postural instability.

Parkinson’s Connection to Basal Ganglia 

• Caused by loss of dopamine neurons in substantia nigra → imbalance of direct/indirect pathways. 

• Results in excessive output filtering, suppressing movement. 

Parkinson’s Treatment 

L-DOPA: precursor to dopamine that can cross blood-brain barrier and boost dopamine synthesis. 

Otto Loewi’s Experiment 

• Otto Loewi stimulated the vagus nerve of a frog heart, which slowed the heart rate. 

• He transferred the solution bathing that heart to a second frog heart. 

• The second heart also slowed, despite no neural connection. 

• This demonstrated that a chemical—later named acetylcholine—was responsible for transmitting signals across the synapse. 

• Loewi's experiment was the first direct evidence of chemical neurotransmission. 

ACh Synthesis 

• ACh is synthesized in the presynaptic terminal from acetyl CoA and choline. 

• The enzyme choline acetyltransferase (ChAT) catalyzes the reaction. 

• ChAT activity is the rate-limiting step of ACh synthesis. 

• ACh is then packaged into synaptic vesicles by the vesicular acetylcholine transporter (VAChT). 

ACh Receptors: Nicotinic and Muscarinic 

• Nicotinic receptors are ionotropic, meaning the receptor is a channel that opens directly when ACh binds. 

• Found in CNS and at neuromuscular junctions. 

• Binding of 2 ACh molecules opens the channel for Na⁺ and K⁺. 

• Net Na⁺ influx leads to depolarization (EPSP). 

• Muscarinic receptors are metabotropic (GPCRs). 

• Found in organs like the heart. 

• Binding of ACh activates G-proteins → beta-gamma subunits open K⁺ channels. 

• K⁺ exits the cell, causing hyperpolarization (IPSP), decreasing heart rate. 

Pharmacology - Nicotinic and Muscarinic

• Nicotinic receptor: 

• Agonist: Nicotine → mimics ACh → EPSPs. 

• Antagonists: Curare and α-bungarotoxin → block ACh binding → no muscle contraction → paralysis. 

• Muscarinic receptor: 

• Agonist: Muscarine (from mushrooms) → causes IPSPs. 

• Antagonist: Atropine → blocks IPSPs, increasing heart activity. 

ACh Inactivation 

• ACh is broken down in the synaptic cleft by the enzyme acetylcholinesterase (AChE). 

• AChE hydrolyzes ACh into acetate and choline. 

• Choline is taken back up into the presynaptic terminal to be reused in ACh synthesis. 

Neuropeptides 

• Synthesized in the cell body, unlike small molecule neurotransmitters. 

• Packaged into dense core vesicles and transported to the terminal. 

• Released after high-frequency stimulation due to higher Ca²⁺ requirements. 

• Act on metabotropic receptors and have longer-lasting effects. 

Endocannabinoids 

• Not stored in vesicles; synthesized on demand in the postsynaptic neuron. 

• Diffuse retrogradely to act on presynaptic CB1 receptors. 

• Inhibit neurotransmitter release—modulate synaptic transmission. 

• Lipid-based molecules (e.g., anandamide). 

Nitric Oxide (NO) 

• Also synthesized on demand from arginine via nitric oxide synthase (NOS). 

• Not stored in vesicles; diffuses freely across membranes. 

• Acts on guanylyl cyclase in target cells to increase cGMP. 

• Plays a role in vasodilation and synaptic plasticity. 

Steps in Chemical Signaling 

• Step 1: Action potential reaches the axon terminal, depolarizing the membrane. 

• Step 2: Voltage-gated calcium channels open; Ca²⁺ floods into the terminal. 

• Step 3: Synaptic vesicles dock at the membrane via SNARE proteins. 

• Step 4: Vesicles fuse and release neurotransmitter into the synaptic cleft (exocytosis). 

• Step 5: Neurotransmitter binds to receptors on the postsynaptic membrane. 

• Step 6: Postsynaptic potentials are generated (EPSPs or IPSPs). 

• Step 7: Neurotransmitter is inactivated via enzymatic degradation, reuptake, or diffusion. 

Presynaptic: What is quantized neurotransmitter release? 

• Quantized release means neurotransmitters are released in discrete packets called quanta. 

• Each quantum corresponds to the contents of one synaptic vesicle. 

• Miniature end plate potentials (mEPPs) reflect spontaneous single-vesicle release. 

• The number of vesicles released during evoked activity varies randomly (follows a binomial distribution). 

• Calcium influx increases the probability of vesicle fusion, but does not guarantee it. 

Postsynaptic: What causes PSPs? How are EPSPs and IPSPs different? 

• PSPs result from neurotransmitter binding to receptors, causing ion channels to open. 

• EPSPs (excitatory): Cause depolarization (cell becomes more positive, more likely to fire). 

• IPSPs (inhibitory): Cause hyperpolarization (cell becomes more negative, less likely to fire). 

• Ions involved include Na⁺ (inward, depolarizing) and Cl⁻ or K⁺ (outward or inward, hyperpolarizing). 

• PSPs occur primarily on dendrites and summate at the axon hillock. 

What is summation? 

• Summation is the process where multiple PSPs combine to influence whether a neuron fires. 

• Temporal summation: Rapid, repeated signals from one synapse add together. 

• Spatial summation: Simultaneous input from multiple synapses adds together. 

• If combined input reaches threshold, it triggers an action potential. 

Ionotropic vs. Metabotropic Receptors 

• Ionotropic receptors: Ligand-gated ion channels; open directly when neurotransmitter binds. 

• Fast and short-acting (milliseconds). 

• Example: Glutamate or GABA receptors. 

• Metabotropic receptors (GPCRs): Do not form channels; activate G-proteins which trigger signaling cascades. 

• Slower onset, longer-lasting effects. 

• Can cause widespread metabolic changes in the neuron. 

What are G-proteins and the G-protein cycle? 

• G-proteins are made of α, β, and γ subunits. 

• Inactive state: Bound to GDP. 

• When activated by a receptor, GDP is replaced by GTP → G-protein becomes active. 

• The α-subunit and βγ-complex then activate downstream effectors (e.g., enzymes or ion channels). 

• The GTP is hydrolyzed back to GDP to inactivate the G-protein. 

Describe the Phospholipase C, IP3, DAG, Protein Kinase C cascade 

• Gαq activates Phospholipase C (PLC). 

• PLC splits PIP₂ into IP₃ and DAG. 

• IP₃ causes release of Ca²⁺ from intracellular stores (ER). 

• DAG stays in the membrane and activates Protein Kinase C (PKC). 

• PKC phosphorylates target proteins, altering neuronal activity and function. 

Compare and contrast passive and active signaling 

• Passive signaling involves small, local voltage changes (e.g., at synapses) that decay as they spread; no ion channel amplification is involved. 

• Active signaling (action potentials) involves voltage-gated ion channels that regenerate the signal, allowing it to travel long distances without decrement. 

• Passive signals are essential for neural computation in dendrites and cell bodies. 

• Active signals are essential for long-distance communication, especially in large or long neurons. 

• Passive signaling decreases with distance like ripples in water, while active signals are all-or-none and self-propagating. 

• Action potentials require a threshold to trigger; passive potentials do not. 

What happens during an action potential? What are its key features? 

• Depolarization Phase: Triggered by threshold voltage, Na⁺ channels open rapidly, causing inward Na⁺ flow. 

• Overshoot: Membrane potential becomes positive inside the cell. 

• Repolarization: Na⁺ channels inactivate; K⁺ channels open, K⁺ flows out. 

• After-hyperpolarization: Membrane becomes more negative than resting due to extra K⁺ outflow. 

• Refractory Periods: 

• Absolute: Na⁺ channels inactivated; no new AP can occur. 

• Relative: Some Na⁺ channels reset; stronger stimulus needed for AP.

How are these features accounted for by Na⁺ and K⁺ channel properties? 

• Na⁺ Channels: Two gates (activation and inactivation). 

• Activation is fast, allowing Na⁺ in. 

• Inactivation is slower, stopping Na⁺ flow—key to brief depolarization. 

• K⁺ Channels: One slower gate; open as Na⁺ channels inactivate. 

• Stay open longer, leading to repolarization and after-hyperpolarization. 

• Timing differences between Na⁺ and K⁺ channel gating explain the shape and sequence of the action potential phases. 

How does the action potential propagate? 

• Initiated at the axon hillock; local depolarization spreads to adjacent areas. 

• Voltage-gated Na⁺ and K⁺ channels open in the next segment, regenerating the signal. 

• This continues like dominoes falling down the axon until it reaches the terminal. 

• Action potentials only move forward due to the refractory state behind the signal—prevents backward activation. 

What influences the speed of propagation? 

• Not affected much by ion channel gating speed or current speed. 

• Main factor: Distance the depolarization spreads passively before needing to be regenerated. 

• Two strategies to increase speed: 

• Larger axon diameter: Less internal resistance, allows further passive spread. 

• Myelination (noted elsewhere in general neuroscience): Increases passive spread and speeds conduction via saltatory conduction.

What is axoplasmic transport and why is it needed? 

• Axoplasmic transport is the movement of materials (organelles, proteins, vesicles) within the axon. 

• It moves materials from the soma to the axon terminal (anterograde) and back (retrograde). 

• This transport is vital because proteins and organelles are made in the soma and need to reach distant axon terminals. 

• Damaged materials are also returned to the soma for recycling. 

• Microtubules act as tracks, and motor proteins like kinesin (anterograde) and dynein (retrograde) use ATP to move cargo along them

What drives ions across the cell membrane? 

• Concentration gradients: Ions move from high to low concentration (diffusion). 

• Electrical gradients: Ions move toward areas of opposite electrical charge. 

• These two combined forces form the electrochemical gradient, which determines the net direction of ion movement. 

• Ions can only move when their specific ion channels are open

What does the Nernst potential calculate? 

• It calculates the equilibrium potential (voltage) for a specific ion. 

• This is the voltage where the electrical gradient exactly balances the concentration gradient, so there is no net ion movement. 

• For example, for Na⁺, it's the point where diffusion inward is exactly offset by the electrical push outward. 

How do the Nernst potentials (for different ions) relate to the membrane potential? 

• Each ion has a different Nernst potential due to its unique intra- and extracellular concentrations. 

• The membrane potential is not equal to any single ion's Nernst potential unless only that ion is permeable. 

• In real neurons (with multiple permeable ions), the resting membrane potential is a weighted average—closer to ions with higher permeability (e.g., usually K⁺). 

What is the Na⁺/K⁺ ATPase? What is its role? 

• The Na⁺/K⁺ ATPase (or pump) is a membrane protein that uses ATP to transport 3 Na⁺ out and 2 K⁺ into the cell. 

• It maintains the Na⁺ and K⁺ concentration gradients required for resting potential and action potentials. 

• It’s electrogenic: it moves more positive charges out than in, contributing directly to the membrane potential. 

• It compensates for passive ion leaks and uses 25–50% of the nervous system’s energy.