Neuroscience: Directionality and Orientation

• The midterm is worth 50 points, which is 10% of final grade
• The midterm covers lectures 1-6b, readings Yuste 1, Yuste 2, Hodgkin & Huxley, and chapters 2 & 3 in Purves/Augustine Neuroscience textbook up to Figure 3.9 (p. 62 in the 7th ed.)

Lecture 1: Directionality & Orientation

• Dorsal: Towards the spine
• Ventral: Toward the belly
• Superior: Towards the top
• Inferior: Towards the bottom
• Anterior: Towards the front
• Posterior: Towards the back
• Rostral-Caudal: Direction towards the nose to the tail
• Medial-Lateral: Direction from the midline to the side
• Horizontal Plane: Divides the brain into top and bottom sections
• Sagittal Plane: Divides the brain into left and right sections
• Coronal Plane: Divides the brain into front and back sections
• Ipsilateral: On the same side of the body
• Contralateral: On the opposite side of the body
• Decussation: Crossing of axons to the contralateral side
• Bilateral: On both sides of the body
• Unilateral: On one side of the body
• Proximal: Close to the trunk
• Distal: Far from the trunk
• Efferent: Away from ("exit" the) central nervous system (CNS)
• Afferent: Towards ("arrive" to) the CNS

Spinal Cord and Matter

• Gray matter consists of neuronal cell bodies
• White matter consists of myelinated axon bundles/tracts

Peripheral Nervous System

• The peripheral nervous system includes 12 pairs of nerves transmitting sensory and/or motor information
• Axons emerge from nuclei in the brainstem and cortex to regulate information flow to and from, internal organs, and specialized sensory systems and muscles in the head and neck

Lecture 2: Neuron Types and Categories

• Sensory neurons receive information from the environment (or the body) through specialized receptors, transmitting action potentials to the spinal cord and brain
• Sensory neuron types include unipolar, bipolar, and pseudounipolar
• Motor neurons control muscle movements
• Interneurons make synaptic connections with sensory and motor neurons in the spinal cord and connect with many other neuron subtypes in the brain

Neurons Based on Connectivity

• Local Inhibitory Neurons: Neocortical Interneurons
• Long-range Inhibitory Neurons: Medium spiny cells of the striatum (GABA) to and from neocortex and Purkinje cells of the cerebellum project to deep cerebellar nuclei
• Local-range Excitatory Neurons: Pyramidal cells are found in neocortex and project to many subcortical areas. Spinal motor neurons project out of the CNS to skeletal muscle
• Neuromodulatory Neurons: Dopaminergic neurons in the substantia nigra project to caudate

Glial Cells

• Glial cells play a role in brain development, growth support, and contribute to neural signaling, metabolism, and immune function
• Astrocytes are present throughout the CNS and surround neurons and capillaries
• Astrocytes help maintain the appropriate chemical environment by participating in neurotransmitter recycling/uptake and synaptic communication, and have neurotransmitter transporters and receptors on their surface
• Astrocytes play a role in synaptic formation and stabilization
• A subset of astrocytes retain stem cell-like characteristics
• Oligodendrocytes are found in the CNS
• A single oligodendrocyte cell can ensheathe axon segments on multiple axons
• Schwann cells are found in the PNS and can only wrap a single region of an axon
• Both oligodendrocytes and Schwann cells produce myelin that plays an important role in neuronal function
• Microglia are phagocytic cells derived from macrophages during development
• Microglia act as scavenger cells, removing cellular debris during phagocytosis following cell death and injury
• Microglia respond to cytokines and regulate inflammation, influencing neuronal survival
• Microglia produce signals that recruit microglia to sites of injury
• Microglia play a role in synapse development
• Ependymal cells line the ventricles, produce cerebrospinal fluid, and form attachments to astrocytes
• Sides of ependymal have cilia that move cerebrospinal that move fluid through the ventricle
• Tanycytes are a specialized ependymal cell found in the third ventricle, are are involved with metabolic sensing and transport of substances into the hypothalamus

Lecture 3: Neuron Components

• Soma is the cell body and contains the nucleus and most of the cytoplasm
• Soma contains high level of euchromatin, mitochondria, endoplasmic reticulum, Golgi apparatus, and structural cytoskeletal proteins
• mRNA moves from the nucleus and are first synthesized in the rough endoplasmic reticulum then move to the golgi
• Axon starts as a single branch and splits far from the soma
• Axon hillock is the bump where the soma turns into the axon
• Axon Initial segment (AIS) is right after the hillock, where axon potentials are first generated
• Axon Terminal is where the neurotransmitter release machinery is located
• Axons contains synaptic vesicles, are 1 - 20 microns in diameter, do not taper after branching
• Organelles in axons are mitochondria, synaptic vesicles, and cytoskeletal elements
• Axons contain specialized proteins like voltage-gated ion channels, cytoskeletal proteins, and motor proteins
• Dendrites taper after branching
• Dendrites contain dendritic spines, post-synaptic specializations, neurotransmitter and voltage-gated ion channels
• Dendrites can be contacted by many axons or multiple synapses from the same axon
• Polysomes and RER are located in dendrites where some translation of specific proteins occur locally
• Over a lifetime, dendrites grow (development), get remodeled (learning), and become thinner with fewer spines (aging)
• Dendritic shaft is the main arm of the dendrite.
• Spine neck is the initial protrusion from the shaft
• Spine head is the round end of the spine
• Subcellular organelles support neurons
• Cytoskeletal elements
• Microtubules are hollow tubes of 25nm in diameter
• Microtubules are dynamic and polarized with varying stability, including many types of microtubules-associated proteins (MAPs)
• Neurofilaments are 4-6nm in diameter and 0.4-0.8 microns long, and are found in presynaptic terminals, dendritic spines, and growth cones of axons
• Neurofilaments are important for neurotransmitter receptor and ion channel localization
• Nissl Substance and Golgi Apparatus

Lecture 4: Electrical Signaling

• Three types of electrical signals in neurons
• Receptor potential is found in all sensory neurons, and are “graded” potentials, meaning they are sensitive to stimulus strength
• Synaptic potential is like receptor potentials, these synaptic responses can vary in size depending on the number and timing of inputs
• Action potentials are electrical responses that do not vary in size once triggered, and will be repeatedly activated with stronger stimuli

Active and Passive Signals

• Passive signals are downward currents, hyperpolarization, dip below resting potential
• Active signals are positive currents, depolarization, and the action potential threshold is reached
• Two types of proteins that set up and maintain the resting membrane potential
• Active transporters use a Sodium-Potassium-ATP Pump
• Ion channel intrinsic permeabilities
• Electrochemical equilibrium
• If membrane is permeable to K+, and there is an equal amount of K+ on both sides of the membrane, there will be no net flux of K+
• Nerst Potential: Eion=58/z log10 [ion]out/[ion]in
• 58mV should be 61mV at mammalian temp
• Resting phase goes to top of ap during rising phase

Neuronal Scale

• Light microscope magnification is x100-x1000
• Electron microscope magnification is x10^4-x10^7

Lecture 5: Nernst and Goldman Equations

• Nernst equation calculates the equilibrium potential for a single ion based on concentration gradient and charge.
• Goldman equation accounts for 3 types of ions and the relative permeabilities of the neuronal membrane
• Hodgkin & Huxley experiments varied external K+ and Na+: the membrane explained by Nerst equation, and extracellular Na reduced action potential but didn't change resting mmebrane potential

Lecture 6a: Permeability and Conductance

• Ohms Law: Voltage (V)= Current (I) X Resistance (R)
• Conductance is a measure of charge flow through a channel and is not dependent on a particular ion
• Membrane potential, Vm varies from -65mV to -70mV

Lecture 6b: Voltage Clamp Experiments

• Used to study ion currents and understand action potentials
• The neuron is at -65mV
• Membrane potential is clamped to 0 mV two major ionic currents appear, Na+ influx then followed by outward current/ k+ efflux
• This helps determine which ions contribute to permeability changes, the bottom row observers how currents change

Hodkin and Huxley

• K+ and Na+ are essential from phase 1 of AP and these channels are voltage sensitive, knowing voltage of the membrane, Na+ won’t open unless they reach threshold, more K+ hyperpolarizes it,
• TTX blocks early inward Na+ currents
• TEA blocks late outward K+ current

Feedback Loops

• AP is a fast positive cycle and a slow negative cycle, and these occur at the same time
• Fast: Depolarization + Na Channels + Increase Na-> Depolarization Slow: Depolarization + Open K Channels + Increase K+ - > Hyperpolarization

Anesthesia

• Local: Blocks Na+ channels, prevents nerve from signaling pain
• Regional: Sedatives relax, act on brain gaba to increase inhibition, (Pentobarbital, Diazepam, Zolpidem and propofol
• General: Causes loss of consciousness

Vocabulary

• membrane conductance describes the allowance of ions
• voltage clamp technique is when researchers measure ionic current

Yuste Reading 1- Brain Prediction Model

• Brain builds model of world via memory
• Leads to action, influences decisions, evolution in nervous system
• Neural circuits do all of the building and system stuff

7 Principles of Neuroscience

• Hierarchy, Neural Ensembles, Wiring, Learning, Optimization, Maps, Contro, Theory
• Neurons are excitatory, inhibitory, vary in function, GABAergic neurons

Yuste Reading 2

• Glutamate is Excitatory and Gabba is inhibitory and there are special neurons in different regions like pyramid, 3 types astrocytes support
• Electrical synapses, ion flow
• Chemical Synapses use neurotransmitters
• Activating GABA receptors, allows chloride in and causes hyperpolarization

Hodgkin and Huxley Reading

• Collaborated, and won noble prize for researching nerve conduction
• Found Squid as new test target
• Depolarization by SOdium and Repolarization by Pottasium
• Used voltage clamp, they also discovered sodium and potassium conductances during those impulses

Overview of directionality and orientation in neuroscience, including anatomical terms like dorsal, ventral, anterior, and posterior. Also covers planes of section (horizontal, sagittal, coronal) and laterality (ipsilateral, contralateral, bilateral, unilateral).