Introduction to Neuroscience Notes

Introduction to Neuroscience

Course Information

• Welcome to Introduction to Neuroscience!
• Professor: B.J. Casey, PhD
  • The Christina L. Williams Professor of Neuroscience.
  • Department of Neuroscience and Behavior, Barnard College.
  • Office: Milbank 226A.
  • Office hours: By email appointment (bcasey@barnard.edu).
• Teaching Assistants (TAs):
  • Rosa I. Caamaño-Tubío, PhD
    • Department of Psychology, CCNY
    • rctubio@ccny.cuny.edu
    • Tuesdays 10-11:00 in Milbank 235
  • David Gruskin, MD PhD student
    • Zuckerman Institute, Columbia
    • dcg3153@cumc.columbia.edu
    • Mondays 2:30-3:30pm via zoom
  • Rachel Estrella, PhD student
    • Columbia University
    • dcg3153@cumc.columbia.edu
    • Wednesdays 3:30-4:30pm via zoom

Course Reminders

• Read the syllabus carefully for assignments, honor code, and resources.
• Always sign in (moving toward QR code); headcounts will also be taken.
• Upcoming exam: February 6th.
• Extra credit assignment available.
• Masks are provided.

Exams

• Exams will be on CourseWorks, in-class.
• Bring a charged laptop.
• Must sign in with ID and sign out.
• Exam Weighting:
  • Exam 1: 15%
  • Exam 2: 20%
  • Exam 3: 20%
  • Exam 4: 20%
  • Exam 5: 25%

Exam Dates

• Exam 1: Thursday, February 6, 8:40 AM
  • Make-up Exam: Friday, February 7 at 10 AM in Milbank 410 (instructor permission required; email verification).
• Exam 2: Thursday, February 27, 8:40 AM
  • Make-up Exam: Friday, February 28 at 10 AM in Milbank 410 (instructor permission required; email verification).
• Exam 3: Thursday, March 27th, 8:40 AM
  • Make-up Exam: Friday, March 28 at 10 AM in Milbank 410 (instructor permission required; email verification).
• Exam 4: Thursday, April 17th, 8:40 AM
  • Make-up Exam: Friday, April 18 at 10 AM in Milbank 410 (instructor permission required; email verification).
• Exam 5: Thursday, May 1st, 8:40 AM
  • Make-up Exam: Friday, May 2nd at 10 AM in Milbank 410 (instructor permission required; email verification).
• Exams are based on readings and lecture slides.
• If you have accommodations, the CARDS or DS offices at Barnard and Columbia will administer your exams.

Extra Credit

• Worth 1 final point to overall grade.
• Due anytime by or before May 2nd.
• Create a creative picture of the brain, brain region, circuit, or cell(s) using no words.
• Use color, candy, produce, flowers, people, objects, etc.
• Submission must be original and not from the internet.
• See syllabus for detailed instructions.
• Sharing during the semester is encouraged (indicate permission when submitting).

Questions

• Bring questions to class, office hours, and/or review sessions.
• Content questions cannot be answered via email.

Nervous Systems

• Many attributes of the nervous system have been conserved across species.
  • Sea slug: learning and memory.
  • Rodent: fear learning.
  • Fly: sleep-wake cycle.

Divisions of the Nervous System

• Central Nervous System (CNS):
  • Neurons reside entirely within the brain and spinal cord.
• Peripheral Nervous System (PNS):
  • Neurons allow the CNS to communicate with the periphery of the body (cranial and spinal nerves).
  • 12 pairs of cranial nerves bypass the spinal cord for direct communication between the brain and the periphery.
  • They send electrical signals between your brain, face, neck, and torso.

Cranial Nerves

• Olfactory nerve: Sense of smell.
• Optic nerve: Ability to see.
• Oculomotor nerve: Ability to move and blink your eyes.
• Trochlear nerve: Ability to move your eyes up and down or back and forth.
• Trigeminal nerve: Sensations in your face and cheeks, taste, and jaw movements.
• Abducens nerve: Ability to move your eyes.
• Facial nerve: Facial expressions and sense of taste.
• Auditory/vestibular nerve: Sense of hearing and balance.
• Glossopharyngeal nerve: Ability to taste and swallow.
• Vagus nerve: Digestion and heart rate.
• Accessory nerve (or spinal accessory nerve): Shoulder and neck muscle movement.
• Hypoglossal nerve: Ability to move your tongue.
• It is important to know their overall general functions and that they bypass the spinal cord.

Cranial Nerve Mnemonic

• Mnemonic example: "On Old Olympus' Towering Top A Finn And German Viewed Some Hops"
• Sensory, Motor, or Both: "Some Say Marry Money, But My Brother Says Big Brains Matter More"

Peripheral Nervous System Divisions

• The peripheral nervous system is divided into somatic and autonomic divisions.

• Somatic Division:

  • Carries information between the CNS and the body parts (nerves to skin to muscle).
  • Allows the brain to receive sensory information and control body movements.

• Autonomic Division:

  • Allows the CNS to communicate with the organs of the body (heart, stomach, intestines) and occurs unconsciously.

Autonomic Nervous System

• Comprised of the:
  • Sympathetic division (Fight or Flight).
  • Parasympathetic division (Rest and Restore).

The Spinal Cord

• Protected by bony vertebrae and three layers of protective tissue called meninges (pia, arachnoid, and dura mater).
• Carries tactile information from the skin up to the brain and sends signals down from the brain to control body movements.
• The central portion is shaped like a butterfly and contains the cell bodies of neurons whose axons can cause muscles to contract.

Spinal Cord: Central Canal

• The central canal runs through the length of the spinal cord and connects to the brain’s fluid-filled ventricles.
• Contains cerebrospinal fluid:
  • Helps keep the brain buoyant.
  • Acts as a cushion from mechanical damage.
  • Assists in maintaining chemical stability.
  • Carries nutrients to the brain.

Neuroanatomy and Neuro Function

• Be familiar with neuroanatomy and neuro function

Planes for Viewing Brain

• Axial: Top to bottom (Superior to inferior).
• Coronal: Front to back (Anterior to posterior).
• Sagittal: Left to right.

Brainstem

• Connects the cerebrum to the spinal cord and cerebellum.
• Composed of three sections: the midbrain, pons, and medulla oblongata.
• Small ( $<3$% of brain) but critical for maintaining life!

Brainstem Functions

• Medulla and pons: critical for maintaining life (respiration, cardiovascular control), sleep and arousal, and basic sensory and motor responses.
• Midbrain contains:
  • Cell bodies of the dopamine neurons that play a key role in reinforcement learning and implicated in addiction and Parkinson’s disease.
  • Superior colliculi: direct attention to visual stimuli.
  • Inferior colliculi: direct attention to auditory stimuli.

Cerebellum

• Derived from cerebrum and means “little brain”.
• Unlike the cerebrum, it spans the midline without interruption.
• Functions:
  • Plays a key role in bodily balance, coordinating body movements, and for moving limbs smoothly and accurately toward their targets.
  • Also involved in timing, temporal prediction, attention, and learning.
  • Implicated in several neurodevelopmental disorders including ADHD.

Cerebellar Ataxia

• Results from damage to cerebellum or its connections
• Case studies:
  • 20 yr old female: loss of balance/dizziness, Late dev milestones: talked/walked 6-7 yrs (Cerebellar agenesis)
  • 5 yr male: distinctive way of speaking, walking; atypical social behavior Late dev milestones: sitting, talking, walking

Thalamus

• Gateway to the Cortex and a Center for Motivation
• Made of 30 nuclei, each of which transmits a specific kind of cognitive (e.g., memory-related), sensory, or motor information to the cortex.
• Described as like a relay station for information.

Hypothalamus

• Important in motivated behaviors (eating, sex, thirst), stress, maintaining body temperature, and sleep/wake cycle.
• Pituitary releases hormones important for growth, metabolism, and reproduction.
• Teaser for lecture on stress and Hypothalamic-Pituitary-Adrenal (HPA) Axis that mediates the effects of stress.

Basal Ganglia

• A collection of brain regions critical for voluntary behaviors such as opening a locked door (e.g., tricky lock w/ practice becomes automatic, habitual, motor memory, implicit).

Limbic System

• Two key components of the limbic system are the amygdala and the hippocampus.
• Amygdala: learns to recognize signs of imminent threat and of emotional significance.
• Hippocampus: critical for storing memories of our experiences (episodic memory).

Cerebral Cortex

• Carries out complex cognitive processes, such as language.

Cerebral Cortex Lobes

• Four lobes of the cerebral cortex:
  • Occipital lobe (vision).
  • Temporal lobe (hearing).
  • Parietal lobe (tactile/sensation).
  • Frontal lobe (movement).
• Fissures and sulci (e.g., longitudinal fissure, central sulcus, and lateral sulcus).

Brain Matter

• Gray matter: cell bodies and dendrites.
• White matter: myelinated axons.
• Ventricles: cerebrospinal fluid (CSF).

Cortical Layers

• The cortex is organized into layers, each with distinct cell types and connections.
• These layers are numbered I-VI.

Imaging Techniques: Spatial and Temporal Resolution

• Invasive and noninvasive imaging techniques have different spatial and temporal resolutions.
• $Spatial Resolution (mm) \propto Temporal Resolution(s)$
• Examples:
  • EEG and MEG.
  • PET imaging.
  • VSD imaging.
  • TMS.
  • fMRI imaging.
  • Brain Microstimulation.
  • 2-DG imaging.
  • Optogenetics.
  • Light microscopy.
  • Calcium imaging.
  • Electron microscopy
    • Patch clamp

Magnetic Resonance Imaging (MRI)

• Based on the perturbation of water molecules in the brain with a radio frequency (RF) pulse within a magnetic field.
• Different tissues in the brain have different amounts of water molecules (e.g., white matter less than gray matter).
• MRI uses powerful magnets which produce a strong magnetic field that forces protons in the body to align with that field.
• When a radiofrequency current is pulsed through the patient, the protons are stimulated and spin out of equilibrium, straining against the pull of the magnetic field.
• When the radiofrequency field is turned off, the MRI sensors can detect the time it takes for the protons to realign with the magnetic field, as well as the amount of energy released, which vary across tissues that are more water or fat.
• Hydrogen atoms are naturally abundant in humans and other biological organisms, particularly in water and fat.
• Pulses of radio waves excite the nuclear spin energy transition, and magnetic field gradients localize the polarization in space.
• By varying the parameters of the pulse sequence, different contrasts may be generated between tissues based on the relaxation properties of the hydrogen atoms therein.

Types of MRI

• Structural MRI (Volume, area, cortical thickness).
• Functional MRI (Activity/Functional).
• Diffusion imaging (Structural Connectivity).

Diffusion Weighted Imaging

• Structural connectivity, index of myelination regularity of fiber tracts (and cell density).
• Can visualize fiber tracts that project in different directions:
  • Superior to Inferior (blue).
  • Right to Left (red).
  • Anterior to posterior (green).

Restriction Spectrum Imaging (RSI)

• Estimating cell density.
• Based on less diffusion of water molecules inside the cell than outside the side.
• The more restricted diffusion, the more cells.
• Has been used to detect neuroinflammation that is associated with gliosis (increase in microglial cells) and decreases in neurons and their dendritic complexity related to stress.

Functional MRI (fMRI)

• Capitalizes on the coupling of cerebral blood flow (CBF), energy demand, and neural activity.
• Blood supplies oxygen to brain cells.
• When these cells are active, there is an increase in blood flow and blood oxygen in the surrounding area.
• fMRI detects the blood oxygen level–dependent (BOLD) changes (oxygenated vs deoxygenated hemoglobin).
• When attend to the right or left of a display, the contralateral side of the primary visual cortex is activated, even when a visual stimulus is presented to both hemispheres simultaneously.

High Field Laminar fMRI

• High Field Laminar fMRI is providing insights into directional information flow in the human brain

Electroencephalogram (EEG)

• Records the electrical signals of the brain by using electrodes attached to your scalp.
• Brain cells communicate with each other using electrical impulses.
• Brain activity can be seen in EEG recordings as wavy lines.
• It’s a snapshot in time of the electrical activity in your brain.

The Human Brain: Key Regions

• Coronal Section:
  1. Cerebrum
  2. Thalamus
  3. Midbrain
  4. Pons
  5. Medulla
  6. Spinal cord
  7. Hippocampus
  8. Caudate (part of basal ganglia)

Cells of the Nervous System

• Neurons and Glia
• Neurons are the fundamental units by which information moves through the nervous system.
• Sights, sounds, thoughts, memories – all depend upon communication between neurons.

Neuron Components

• Dendrites: receive information.
• Cell body: collects information.
• Axon: transmits an electrical signal to the terminal.
• Cell nucleus: contains genetic DNA.

Neurotransmission

• Neurons release neurotransmitters that cross a synaptic cleft to communicate with receiving neurons.
• The neuron sends an electrical signal down its axon and then releases a neurotransmitter from terminals into the synaptic cleft.
• The neurotransmitter binds to receptors on dendrites of a receiving neuron, which may cause that neuron to send a signal down its axon.
• The communication between neurons is called neurotransmission.

Glial Cells

• Glia are being discovered to contribute to other surprising functions, such as learning.

Types of Glial Cells

• Oligodendrocytes
• Schwann cells
• Microglia
• Astrocytes
• Radial glia

Review: Peripheral Nervous System

• Comparison of Somatic and Autonomic Systems
  • Sympathetic
    • Fight or Flight
  • Parasympathetic
    • Rest and Digest

Glial Cells Details

• Oligodendrocytes: form the myelin that surrounds axons of the central nervous system.
• Schwann cells: produce myelin in the peripheral nerves that target body parts and organs.
• Microglia: remove the debris left behind by neurons that are damaged or dead.
• Astrocytes: store substances (e.g., nutrients) for future use by nearby neurons & important in blood-brain barrier.
• Radial glia: form a kind of structure or ‘scaffolding’ that helps guide newly born neurons to their final destinations in the brain.

Oligodendrocytes

• The main function is insulation (myelination) of the axons of the nerve cells in the CNS.
• A single cell can be wrapped around several axons.
• Signal transduction through a myelinated axon is faster.
• Since myelin is a white color substance, it forms the white matter in the brain.
• The myelinated surfaces on the axons are called internodes. The non-myelinated surfaces of the axon are called the nodes of Ranvier.

Schwann Cells

• Insulate (myelinate) and supply nutrients to only one axon of neurons in the peripheral nervous system (PNS).
• Involved in maintenance and regeneration of motor and sensory neurons of the PNS.

Microglia

• Act as the brain's own dedicated immune system, which is necessary since the blood brain barrier isolates the brain from the rest of your body.
• Alert to signs of injury and disease. When they detect it, they charge in and take care of the problem—whether it means clearing away dead cells or getting rid of a toxin or pathogen.
• Implicated in learning-associated plasticity and guiding the development of the brain, detecting unnecessary synapses and "pruning" them.
• Microglia scavenge CNS for damaged neurons, infectious agents, or foreign substances and phagocytoses (devours) them!

Astrocytes

• The internal structure is star-like.
• Tiny protrusions of the cell form a cloud-like region that surround all nearby synapses. These cells store nutrients for nearby cells.

Blood-Brain Barrier (BBB)

• Formed primarily from tight junctions between endothelial cells (cells that line the walls of blood vessels).
• End-feet from astrocytes extend to surround blood vessels and provide support to the endothelial cells of the blood-brain barrier).
• The blood-brain barrier (BBB) is a crucial immunological feature of the bloodstream that prevents any random chemicals circulating in blood from entering the brain.

Radial Glia

• Provide scaffolding for developing neurons, that guide young brain cells into place as brain forms.

How Neurons Work

• When a neuron sends a signal to another neuron, the signal typically moves along parts of the neuron in the following order:
  • Dendrites
  • Cell body
  • Axon
  • Axon terminal
• When the signal reaches the terminal, a neurotransmitter is released, and crosses a synaptic cleft.

Neuronal Activation

• Neurons are activated by the entry of sodium ions ($Na^+$
• The ability of $Na^+$ to enter the neuron plays a key role in neuronal activation.
• Neuronal activation is critical for thoughts, emotions, and behavior.

Ion Concentrations

• High concentrations of sodium ($Na^+$) and chloride ($Cl^−$) ions outside the neuron in the extracellular fluid.
• Inside the neuron are large, negatively charged proteins ($Prot^−$) and potassium ions ($K^+$

Sodium Channels

• Sodium channels are located within the membrane that surrounds the neuron (orange).
• When the channels open, sodium ions ($Na^+$) can move from the extracellular fluid to the inside of the neuron (intracellular fluid).
• A thin cell membrane separates the inside and outside of the cell.
• At rest, the membrane potential (charge inside vs outside) is negatively charged.

Forces Driving Sodium Entry

• Two factors cause sodium to pass through ion channels when they open:
  • Diffusion
  • Electrostatic pressure