Neuroscience Study Guide · NEUR 1520

U1 · Neuroscience perspective + brain anatomy

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CH 01

Neuroscience: Past, Present, and Future

CH 14

Brain Control of Movement

CH 15

Chemical Control of the Brain and Behavior

Lobes of the human cerebral cortex — **Cerebral cortex lobes** — frontal (motor + executive) · parietal (somatosensation + spatial) · temporal (auditory + memory) · occipital (visual). *(Wikimedia Commons, public domain)*

Levels of analysis: Molecular → cellular → systems → behavioral → cognitive. Each level constrains the others.
Central nervous system (CNS): Brain + spinal cord. Encased in bone (cranium + vertebral column), bathed in CSF.
Peripheral nervous system (PNS): Cranial + spinal nerves + autonomic ganglia outside CNS.
Major brain divisions: Telencephalon (cerebrum, basal ganglia) · diencephalon (thalamus, hypothalamus) · mesencephalon (midbrain) · metencephalon (pons, cerebellum) · myelencephalon (medulla).
Cerebral cortex lobes: Frontal (motor + executive), parietal (somatosensation, spatial), temporal (auditory + memory + face), occipital (visual). Insula, cingulate sit deeper.
Anatomical planes: Sagittal (left-right), coronal/frontal (front-back), horizontal/axial (top-bottom). Rostral=anterior, caudal=posterior.
Gray vs white matter: Gray = cell bodies + dendrites + synapses. White = myelinated axon tracts.
Ventricles: Lateral (×2) → third → cerebral aqueduct → fourth → central canal. Choroid plexus produces CSF.

U2 · Neurons + glia

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CH 02

Neurons and Glia

Multipolar neuron with labeled dendrites, soma, axon, myelin sheath, and terminals — **Multipolar neuron** — dendrites receive input · soma houses nucleus · axon hillock initiates AP · myelin (oligodendrocyte/Schwann) speeds conduction · terminals release NTs. *(Wikimedia Commons, public domain)*

Neuron doctrine: Cajal: nervous system = discrete cells communicating across gaps (synapses). Defeated Golgi's reticular theory.
Soma: Cell body containing nucleus + organelles. Site of protein synthesis (Nissl bodies = stacks of rough ER).
Dendrite: Branched input region; receives synapses; spines on excitatory contacts.
Axon: Output process. Single per neuron. Initiates action potential at axon hillock; conducts to terminals.
Axon hillock / initial segment: High density of voltage-gated Na⁺ channels — site of AP initiation.
Neuron classifications: By shape: unipolar, bipolar, multipolar. By function: sensory (afferent), motor (efferent), interneuron.
Astrocyte: Star-shaped glia. K⁺ buffering, glutamate uptake (EAAT), tripartite synapse, BBB end-feet, lactate shuttle to neurons.
Oligodendrocyte: CNS myelinator; one cell wraps multiple axons.
Schwann cell: PNS myelinator; one cell wraps one axon segment.
Microglia [Chivero focus]: CNS-resident immune cells. Phagocytose debris + dead cells; respond to injury + infection. Activated states: M1 pro-inflammatory vs M2 anti-inflammatory. Drive neuroinflammation in HIV, methamphetamine, neurodegeneration.
Ependymal cells: Ciliated cells lining ventricles + central canal. Choroid plexus produces CSF.
Blood-brain barrier (BBB): Tight junctions between brain capillary endothelial cells (claudin-5, occludin, ZO-1) + astrocyte end-feet + pericytes. Excludes most polar/large molecules.

U3 · Membrane potential

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CH 03

The Neuronal Membrane at Rest

CH 04

The Action Potential

Ion gradients (typical mammalian neuron): Inside: high K⁺ (~140 mM), low Na⁺ (~10 mM), low Cl⁻ (~10 mM), low Ca²⁺ (~100 nM). Outside: opposite.
Resting membrane potential: ~−65 mV (range −60 to −80 mV in different neurons). Set primarily by K⁺ permeability through leak channels.
Nernst equation: E_ion = (RT/zF) ln([out]/[in]). At 37°C: E_K ~ −85 mV, E_Na ~ +60 mV, E_Cl ~ −65 mV, E_Ca ~ +120 mV.
Goldman-Hodgkin-Katz equation: V_m = (RT/F) ln[(P_K[K]_o + P_Na[Na]_o + P_Cl[Cl]_i) / (P_K[K]_i + P_Na[Na]_i + P_Cl[Cl]_o)]. Weighted by permeabilities.
Why is V_m close to E_K?: Resting membrane is most permeable to K⁺ (open leak K⁺ channels). V_m drifts toward whichever ion has the highest permeability.
Na⁺/K⁺-ATPase: Maintains gradients: 3 Na⁺ out + 2 K⁺ in per ATP. Electrogenic — contributes ~−5 to −10 mV directly.
Equilibrium vs steady state: At E_ion, no net flux for that ion (reversal potential). Resting V_m is steady state — pumps balance leakage.

U4 · Action potential

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CH 04

The Action Potential

Action potential time-course showing depolarization, peak, repolarization, and afterhyperpolarization — **Action potential** — Na⁺ influx depolarizes (rising phase) · K⁺ efflux repolarizes · refractory period set by Na⁺ inactivation. Threshold ≈ −55 mV; peak ≈ +40 mV. *(Wikimedia Commons, public domain)*

Action potential definition: All-or-none rapid depolarization (~100 mV swing) lasting ~1-2 ms; propagates without decrement along axon.
Threshold: ~−55 mV. Voltage-gated Na⁺ channel opening exceeds K⁺ leak → positive feedback → AP.
Voltage-gated Na⁺ channel: Three states: closed (resting), open (activated), inactivated (ball-and-chain). Inactivation explains absolute refractory period.
Voltage-gated K⁺ channel: Slower activation (delayed rectifier). Repolarizes membrane → afterhyperpolarization. No fast inactivation.
Phases of AP: (1) Rising: Na⁺ in. (2) Overshoot: peaks ~+30 to +40 mV. (3) Falling: Na⁺ inactivates, K⁺ out. (4) Undershoot/AHP: V_m below rest until K⁺ closes.
Absolute refractory period: ~1 ms; Na⁺ channels inactivated, no AP possible regardless of stimulus.
Relative refractory period: ~2-4 ms; some Na⁺ channels still inactivated + AHP — stronger stimulus required.
Saltatory conduction: AP "jumps" between nodes of Ranvier in myelinated axons. ~10-50× faster than unmyelinated of same diameter.
Conduction velocity factors: ↑ axon diameter → ↑ velocity (less internal resistance). Myelin → much faster (saltatory).
Tetrodotoxin (TTX): Pufferfish toxin; blocks voltage-gated Na⁺ channels → no AP. Classic experimental tool.

U5 · Synaptic transmission

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CH 05

Synaptic Transmission

Chemical synapse showing presynaptic terminal with vesicles, synaptic cleft, and postsynaptic receptors — **Chemical synapse** — Ca²⁺ enters presynaptic terminal · vesicles fuse via SNARE complex · NT diffuses across cleft · binds postsynaptic ligand-gated or GPCR receptor. *(Wikimedia Commons, public domain)*

Electrical synapse: Gap junction (connexons) between cells. Bidirectional, fast, no delay. Coupling for synchronized firing.
Chemical synapse — sequence: (1) AP arrives at terminal. (2) Voltage-gated Ca²⁺ channels open. (3) Ca²⁺ triggers vesicle fusion via SNAREs + synaptotagmin. (4) NT released into cleft. (5) Binds postsynaptic receptors. (6) Termination by reuptake/enzyme/diffusion.
Vesicle fusion proteins: v-SNARE synaptobrevin (VAMP) + t-SNAREs syntaxin + SNAP-25 form 4-helix bundle. Ca²⁺ sensor: synaptotagmin.
EPSP: Excitatory postsynaptic potential — depolarizing (e.g., glutamate → cation influx through AMPA/NMDA).
IPSP: Inhibitory postsynaptic potential — hyperpolarizing (e.g., GABA → Cl⁻ influx through GABA_A; or K⁺ efflux through GABA_B-coupled GIRK).
Spatial vs temporal summation: Spatial: multiple synapses simultaneously. Temporal: rapid trains from one synapse. Both bring the soma toward AP threshold.
Ionotropic vs metabotropic receptor: Ionotropic = ligand-gated ion channel (fast, ms). Metabotropic = GPCR → 2nd messenger (slow, seconds, modulatory).
Long-term potentiation (LTP): Sustained increase in synaptic strength. Classic NMDA-dependent LTP in hippocampal CA1: Ca²⁺ through NMDA → CaMKII → AMPA insertion. Cellular basis of memory.
Long-term depression (LTD): Sustained decrease in synaptic strength. Modest Ca²⁺ rise → phosphatases → AMPA internalization.

U6 · Neurotransmitters

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CH 06

Neurotransmitter Systems

Glutamate: Major excitatory NT in CNS. Receptors: AMPA (fast Na⁺/K⁺), NMDA (Ca²⁺, Mg²⁺ block, voltage-dependent), kainate, mGluRs.
GABA: Major inhibitory NT in CNS. Synthesized from glutamate by GAD. Receptors: GABA_A (Cl⁻ ionotropic), GABA_B (GPCR → K⁺ open + Ca²⁺ close).
Glycine: Inhibitory in spinal cord + brainstem. Cl⁻ channel. Strychnine antagonist.
Acetylcholine (ACh): NMJ + autonomic + brain (cholinergic basal forebrain). Receptors: nicotinic (ionotropic, Na⁺/K⁺) + muscarinic (GPCR).
Dopamine (DA): Motivation, reward, motor (substantia nigra → striatum). 5 receptor subtypes (D1-D5), all GPCRs. Implicated in Parkinson, addiction, schizophrenia.
Norepinephrine (NE): Arousal, attention, autonomic. Locus coeruleus (CNS). α + β adrenergic receptors (GPCRs).
Serotonin (5-HT): Mood, sleep, appetite. Raphe nuclei. ~14 receptor subtypes (mostly GPCR; 5-HT3 ionotropic).
Histamine: Wakefulness. Tuberomammillary nucleus. H1-H4 receptors.
Endocannabinoids: Retrograde messengers (anandamide, 2-AG). Activate presynaptic CB1 → reduce NT release.
Nitric oxide (NO): Gas messenger, diffuses freely. Made by nNOS; activates soluble guanylyl cyclase → cGMP.
Neuropeptides: Larger NT (e.g., substance P, enkephalin, oxytocin, neuropeptide Y). Synthesized in soma, transported in dense-core vesicles, GPCR signaling.

U7 · Sensory + Somatosensory system

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CH 12

The Somatic Sensory System

CH 07

The Structure of the Nervous System

CH 10

The Central Visual System

Sensory transduction: Conversion of stimulus energy into electrical signals (receptor potential).
Receptor classes: Mechanoreceptors (touch, hearing), thermoreceptors, photoreceptors, chemoreceptors, nociceptors (pain).
Receptive field: Region of stimulus space (skin area, retinal location) that affects a sensory neuron's firing.
Adaptation: Slowly adapting (SA) receptors fire continuously to maintained stimulus; rapidly adapting (RA) fire on changes.
Touch receptors of glabrous skin: Meissner (RA, fluttering touch) · Pacinian (RA, vibration deep) · Merkel (SA, pressure + form) · Ruffini (SA, skin stretch).
Dorsal column–medial lemniscus pathway: Fine touch, vibration, proprioception. 1st neuron → ipsilateral dorsal columns → gracile/cuneate nucleus (medulla) → DECUSSATES → medial lemniscus → VPL thalamus → S1 cortex.
Spinothalamic (anterolateral) pathway: Pain, temperature, crude touch. 1st neuron synapses in dorsal horn → DECUSSATES at spinal level → ascends contralaterally → VPL thalamus → S1.
Sensory homunculus: Distorted body map in S1 with overrepresentation of hands + face. Penfield's stimulation studies.

U8 · Pain & nociception

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CH 12

The Somatic Sensory System

Aδ fibers: Thinly myelinated, fast (5-30 m/s); sharp, well-localized "first" pain.
C fibers: Unmyelinated, slow (0.5-2 m/s); dull, throbbing "second" pain; longer-lasting.
TRPV1: Capsaicin + heat (>43°C) receptor on nociceptors. Cation channel.
Gate control theory (Melzack-Wall): Aβ touch fibers activate dorsal horn inhibitory interneurons → "gate" partially closes pain transmission. Why rubbing reduces pain.
Periaqueductal gray (PAG): Midbrain center for descending pain modulation; activates raphe + locus coeruleus → spinal inhibition. Endogenous opioid system.
Endogenous opioids: Endorphins, enkephalins, dynorphins. Bind μ, δ, κ opioid receptors → presynaptic + postsynaptic inhibition of pain pathway.
Hyperalgesia vs allodynia: Hyperalgesia = exaggerated pain to noxious stimulus. Allodynia = pain from normally non-painful stimulus (light touch).

U9 · Vision

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CH 09

The Eye

CH 10

The Central Visual System

Schematic diagram of the human eye showing cornea, lens, retina, fovea, optic nerve — **Human eye** — light: cornea → pupil → lens → retina · rods (low light) + cones (color, packed in fovea) → bipolar → ganglion cells → optic nerve. *(Wikimedia Commons, CC-BY-SA)*

Eye optics: Cornea (~⅔ refraction) + lens (variable). Pupil = aperture; iris controls. Retina at back has receptors.
Photoreceptors: Rods (high sensitivity, low resolution, peripheral, scotopic) · cones (low sens, high res, central, photopic, color). 3 cone types (S/M/L; "blue/green/red").
Phototransduction: Dark: cGMP holds CNG channel open → Na⁺/Ca²⁺ in → photoreceptor depolarized → glutamate released. Light: rhodopsin → transducin → PDE → ↓ cGMP → channel closes → hyperpolarization → ↓ glutamate.
Retinal cell layers: Photoreceptor → bipolar → ganglion (output). Horizontal + amacrine = lateral interactions. Light enters from ganglion side.
Center-surround receptive field: ON-center: light in center excites, surround inhibits. OFF-center: opposite. Computed by horizontal cell lateral inhibition.
Retinal ganglion cell axons: Optic nerve → optic chiasm (decussation of nasal fibers) → optic tract → LGN of thalamus → V1 (primary visual cortex).
Magnocellular vs parvocellular: M: large, fast, motion + low contrast. P: small, slow, color + form, high acuity. Parallel processing.
Dorsal vs ventral stream: Dorsal "where/how" = parietal, motion + spatial. Ventral "what" = temporal, object + face recognition.

U10 · Audition + vestibular

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CH 11

The Auditory and Vestibular Systems

Anatomy of the human ear showing outer, middle, and inner ear with cochlea and semicircular canals — **Ear anatomy** — outer (pinna + canal) → middle (tympanum + ossicles) → inner (cochlea = hearing, semicircular canals = vestibular). Hair cells in organ of Corti transduce sound. *(Wikimedia Commons, CC-BY-SA)*

Outer ear: Pinna, ear canal → tympanic membrane (eardrum).
Middle ear: Ossicles malleus → incus → stapes (oval window). Impedance matching air → fluid (×22 amplification).
Cochlea: Spiral fluid-filled tube (3 chambers: scala vestibuli, scala media, scala tympani). Basilar membrane runs length.
Organ of Corti: On basilar membrane. Inner hair cells (sensory; ~3,500) + outer hair cells (motile, amplify; ~12,000). Tectorial membrane on top.
Tonotopic organization: Base of cochlea = high frequency; apex = low frequency. Maintained through auditory pathway up to A1 cortex.
Mechanotransduction: Stereocilia bending → tip-link tension → mechanically gated cation channel opens → K⁺ + Ca²⁺ in → depolarize hair cell → glutamate to spiral ganglion neurons.
Auditory pathway: Hair cell → spiral ganglion → cochlear nucleus → superior olive (sound localization) → inferior colliculus → MGN of thalamus → A1 (Heschl's gyrus).
Sound localization: Interaural time difference (ITD; low freq, medial superior olive) + interaural level difference (ILD; high freq, lateral superior olive).
Vestibular system: Semicircular canals (3, angular acceleration via cupula + ampulla) + otolith organs (utricle + saccule, linear accel + gravity via otoconia on macula). Hair cells transduce.

U11 · Chemical senses

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CH 08

The Chemical Senses

CH 15

Chemical Control of the Brain and Behavior

Olfactory receptor neurons: Bipolar neurons in nasal epithelium. Cilia have GPCR olfactory receptors → G_olf → AC → cAMP → CNG channel → depolarization.
OR gene family: ~400 functional ORs in humans (largest gene family). Each ORN expresses one OR.
Olfactory glomerulus: All ORNs expressing the same OR converge on ~2 glomeruli in olfactory bulb. Mitral cells → piriform cortex (no thalamus relay!).
5 taste modalities: Sweet, salty, sour, bitter, umami. Sweet/bitter/umami via GPCRs (T1R, T2R) → α-gustducin. Salty + sour via ion channels (ENaC, TRP).
Taste pathway: Taste bud → CN VII (anterior 2/3 tongue), IX (posterior 1/3), X (epiglottis) → solitary nucleus (medulla) → VPM thalamus → gustatory cortex (insula).

U12 · Motor systems intro

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CH 13

Spinal Control of Movement

CH 14

Brain Control of Movement

Spinal cord cross-section showing ascending and descending tracts — **Spinal cord tracts** — descending corticospinal carries voluntary motor commands · ascending dorsal columns + spinothalamic carry sensory back to brain. *(Wikimedia Commons, CC-BY-SA)*

Lower motor neuron (LMN): Final common pathway: cell body in ventral horn or brainstem motor nuclei → axon → muscle. Lesion → flaccid paralysis, atrophy, fasciculations.
Upper motor neuron (UMN): Originates in motor cortex; descends via corticospinal tract; synapses on LMN. Lesion → spastic paralysis, hyperreflexia, Babinski sign.
Motor unit: One LMN + all muscle fibers it innervates. Size principle: smaller units recruited first.
Stretch reflex (myotatic): Muscle spindle (Ia afferent) → monosynaptic excitation of homonymous motor neuron + reciprocal inhibition of antagonist via Ia interneuron. Knee jerk.
Golgi tendon organ reflex: Ib afferent senses tension → inhibits its own motor neuron. Protects against overload.
Withdrawal reflex: Polysynaptic; flexor activation + crossed extension contralateral.
Corticospinal tract: M1 → internal capsule → cerebral peduncle → medulla pyramids → DECUSSATES → lateral corticospinal tract → ventral horn LMN. Lateral = limbs; ventral = trunk.
Basal ganglia: Caudate, putamen, globus pallidus, subthalamic, substantia nigra. Direct (D1, GO) + indirect (D2, NO-GO) pathways. Parkinson = SNc dopamine loss; Huntington = caudate degeneration.
Cerebellum: Coordination, balance, motor learning. Three peduncles. Purkinje cell GABAergic output to deep cerebellar nuclei. Lesions → ataxia, dysmetria.

U13 · Glia & neuroinflammation — Chivero focus

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CH 02

Neurons and Glia

Microglia origin: Yolk-sac-derived; resident macrophages of CNS. Distinct from infiltrating monocytes.
Microglial activation states: "M1" pro-inflammatory (TNFα, IL-1β, ROS) vs "M2" anti-inflammatory/restorative (IL-10, TGF-β). Spectrum, not binary.
NLRP3 inflammasome: Cytosolic multiprotein complex. Two-signal activation: priming (TLR → NF-κB → upregulates components) + activation (DAMPs/PAMPs → assembly). Recruits ASC + procaspase-1 → cleaves IL-1β + IL-18 + gasdermin D → pyroptosis. Chivero's research target.
HIV-Tat in neuroinflammation: HIV-1 Trans-activator of transcription crosses BBB; activates microglia; primes NLRP3; contributes to HAND (HIV-associated neurocognitive disorder) even on suppressive ART. Chivero's research.
Methamphetamine + microglia: Meth crosses BBB, activates microglia + induces oxidative stress + NLRP3 priming. Synergistic with HIV in dual-exposed individuals. Chivero's research.
Astrocyte tripartite synapse: Astrocyte processes ensheath synapses; take up glutamate (EAAT1/2), release gliotransmitters (glutamate, ATP, D-serine). Buffer K⁺.
Reactive astrocytosis: Astrocytes upregulate GFAP, hypertrophy, form glial scar after injury. A1 (neurotoxic) vs A2 (neuroprotective) phenotypes.
Microglial pruning: Complement-tagged synapses (C1q, C3) phagocytosed by microglia during development + aging + Alzheimer.
Neurodegeneration + microglia: Alzheimer (TREM2, complement), Parkinson (α-syn-activated), ALS, MS — chronic microglial activation contributes to pathology.

U14 · Pharmacology & drugs of abuse

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CH 15

Chemical Control of the Brain and Behavior

Agonist vs antagonist: Agonist binds + activates receptor. Antagonist binds + blocks. Inverse agonist reduces constitutive activity.
Allosteric modulator: Binds non-orthosteric site → potentiates (PAM) or inhibits (NAM) agonist effect. Benzodiazepines = PAM at GABA_A.
Mesolimbic dopamine pathway: VTA → nucleus accumbens (NAc) + PFC. Final common reward circuit; activated by virtually all addictive drugs.
Cocaine: Blocks DAT, NET, SERT → ↑ synaptic monoamines. Strong reinforcer via NAc DA.
Amphetamine + methamphetamine: Reverses DAT (efflux), enters vesicles displacing DA. Massive ↑ extracellular DA. Neurotoxic at high doses (oxidative stress, microglia).
Opioids: μ receptor agonists → presynaptic Ca²⁺ ↓ + postsynaptic K⁺ ↑ → inhibition. Analgesia + euphoria + respiratory depression.
Alcohol: Enhances GABA_A + inhibits NMDA → sedation. Chronic → withdrawal hyperexcitability + addiction.
Nicotine: Nicotinic ACh receptor agonist; α4β2 on VTA DA neurons → NAc reward.
Cannabis (THC): CB1 agonist; presynaptic; reduces NT release. Affects memory (hippocampus), motor (basal ganglia), reward.
Tolerance: Reduced response after repeated exposure. Pharmacodynamic (receptor downregulation) + pharmacokinetic (faster metabolism).
Sensitization: Increased response with repeated exposure (especially psychomotor stimulants).
Addiction circuits: VTA → NAc + amygdala + PFC; loss of top-down PFC control + amygdala stress dysregulation. Chivero's lab studies SUD-microglia interactions.

U15 · Methods + integration

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CH 21

-One The Resting Brain, Attention, and Consciousness

CH 25

-five Molecular Mechanisms of Learning and Memory

EEG: Scalp electrodes record summed dendritic potentials. Excellent temporal (ms), poor spatial. Frequency bands: δ, θ, α, β, γ.
fMRI: BOLD signal — blood oxygenation. Good spatial (~mm), poor temporal (~seconds). Indirect measure of activity.
Patch clamp: Glass pipette suction onto cell membrane → record currents from individual ion channels (single-channel) or whole cell.
Intracellular vs extracellular recording: Intra: pipette inside cell; measures V_m + APs + synaptic potentials. Extra: outside; only spikes resolved.
Optogenetics: Express channelrhodopsin (ChR2, Na⁺ in, excitation) or halorhodopsin (Cl⁻ in, inhibition) → light-triggered control of neurons in vivo.
Chemogenetics (DREADDs): Designer GPCRs (hM3Dq, hM4Di) activated by clozapine-N-oxide → minute-scale modulation.
Calcium imaging: GCaMP fluoresces with Ca²⁺. Bulk or single-cell readout of activity over time.
Lesion studies: Loss of function via surgical, chemical, or pharmacological ablation → infer normal role.

Chivero-targeted exam tips

Be ready to diagram an action potential with phases + ion movements + channel states.
Know NLRP3 inflammasome: priming → activation → caspase-1 → IL-1β + gasdermin D → pyroptosis.
For each NT system: synthesis enzyme, source nucleus, receptor types, behavioral role.
Sensory pathways — DC-ML vs spinothalamic vs visual — be able to draw decussation point + relay nuclei.
Watch for Chivero's HIV-Tat / methamphetamine / microglia framing on standard topics.

📚 Textbook companion · Bear Neuroscience Enhanced

Each unit above maps to chapters in the locally-OCR'd Bear Neuroscience Enhanced. Use the cards below as a quick visual jump into the embedded textbook reader — one figure per chapter, click to read the full chapter: