Behavioral Neuroscience Notes

What is Neuroscience?

• The study of the structure and function of the nervous system.

What is Behavioral Neuroscience?

• It studies the relationship between the nervous system and behavior.
• The nervous system includes:
  • Central Nervous System:
    • Brain
    • Spinal cord
  • Peripheral Nervous System:
    • Ganglion
    • Nerves

How do humans produce behaviors?

• Two perspectives:
  • Dualism:
    • Mind is separate from the brain.
    • Historical perspective.
  • Monism:
    • Mind is produced by the brain.
    • Modern perspective.

What exactly is behavior (Psychological Perspective)?

• Psychology is the scientific study of behavior.
  • The scientific study of all overt activities of the organism as well as all the internal processes that are presumed to underlie them (e.g., learning, memory, motivation, perception, emotion).

What is behavior?

• Thoughts, sensations, and actions.
• Sensing our environment.
• Basic Biological Functions.
• Movement.
• Emotions.
• Language.
• Problem Solving.

Alternative Perspective of Behavior

• The nervous system performs functions that all support a single primary function: control of movement (overt actions of the organism).

Everyone knows what behavior is but they just don't agree on it

• Large-scale quantitative survey about the meaning of behavior across academic disciplines
• Identified discrete definitions of behavior
• Individuals have consistent definitions
• Different disciplines use different definitions for the word "behavior"

Behavioral Neuroscience: Reductionism and Generalization

• Reductionism: Seeking to interpret complex phenomena in terms of simpler phenomena.
• Generalization: Seeking universal or general explanations.
• We seek simple explanations while also keeping in mind the challenges of generalization:
  • Model organisms are helpful for studying basic neurobiological processes and isolating variables.
  • But, differences between species and situations raise important experimental and conceptual considerations.

Behavioral Neuroscience: Interdisciplinary

• Draws from many fields.
• Considers many levels of information.
• The class is organized by level:
  • Unit 1: Intro & Cellular level
  • Unit 2: Systems level
  • Unit 3: Behavioral & Cognitive level

Intro to Methodology & Anatomy

• Lecture Content
  • Methodological Considerations
  • External Anatomy
  • Central Nervous System
  • Peripheral Nervous System
  • Anatomical directions and planes

Methodological Considerations: Evolutionary Perspective

• Comparative anatomy
  • Shared functions
  • Model

Methodological Considerations

• Evolutionary perspective
• Comparative anatomy
• Shared functions
• Model
• Loss of function
• Damage (lesion/ablation)
• Disease or disorder (clinical case studies)
• Experimental
• Correlation
  • Measuring behavior AND neural function
• Manipulate
  • Change neural function AND measure behavior

Overall anatomical organization

• Different parts of a neuron
  • Nucleus
  • Cell body
  • Axon
  • Telodendria
  • Axon hillock
  • Synaptic terminals
  • Golgi apparatus
  • Endoplasmic reticulum
  • Mitochondrion
  • Dendrite
  • Dendritic branches

External Anatomy of the brain

• 2 hemispheres
• Gyri (or gyrus) = Bumps
• Sulci (or sulcus) = Small grooves

External Anatomy of the nervous system

• Brain
  • Central nervous system (CNS)
• Spinal cord
  • Central nervous system (CNS)
• Nerves
  • Peripheral nervous system (PNS)

Two major divisions of the nervous system

• Central Nervous System (CNS)
  • Brain
  • Spinal cord
  • Encased in bone
• Peripheral Nervous System (PNS)
  • Cranial & spinal nerves

Divisions of the Nervous System

• Nervous System
  • Central Nervous System
    • Brain
    • Spinal Cord
  • Peripheral Nervous System
    • Autonomic Nervous System
      • Afferent (sensory) nerves
      • Efferent (motor) nerves
      • Parasympathetic Nervous System
      • Sympathetic Nervous System
    • Somatic Nervous System
      • Afferent (sensory) nerves
      • Efferent (motor) nerves

The Brain

• Made up of cells and floats in a pool of cerebrospinal fluid (CSF).
• Requires a large blood supply but is chemically protected by the blood-brain barrier.

Circulatory system

• Artery -> Capillary -> Vein

The Brain and the Meninges

• The brain is made up of cells and floats in a pool of cerebrospinal fluid (CSF).
• 3 membranes: Dura mater, Arachnoid membrane, Pia mater

The spinal cord is also covered by meninges

• Pia mater
• Arachnoid mater
• Dura mater
• Spinal meninges

Cerebrospinal Fluid (CSF)

• Functions:
  • Acts as a cushion or "shock absorber”
  • Helps deliver nutrients to the brain and remove waste
  • Maintains intracranial pressure with blood volume; can compensate for changes in brain size and blood volume

CSF in The 4 Cerebral Ventricles

• Lateral ventricles
• Third ventricle
• Cerebral aqueduct
• Fourth ventricle
• Central canal
• Ventricles are fluid-filled cavities in the bran

The flow of CSF- from Ventricles to Meninges

• Lateral Ventricles -> third ventricle -> cerebral aqueduct -> fourth ventricle -> subarachnoid space->

The flow of CSF continued

• CSF is found in the cerebral ventricles, subarachnoid space, and central canal in spinal cord
• Produced by the choroid plexus in the ventricles: network of capillaries (small blood vessels) that protrude into ventricles.
• Absorbed in arachnoid granulations in the sinuses: cavities lined by dura matter and filled with venous blood, which drains into veins of the neck (jugular veins) and helps remove waste.
• Blockade of the flow of CSF produces hydrocephalus

Hydrocephalus

• Build up of CSF that leads to expanded ventricles
• Can produce brain damage if left untreated
• Treated with shunt tube

Divisions of the Nervous System

• Nervous System
  • Central Nervous System
    • Brain
    • Spinal Cord
  • Peripheral Nervous System
    • Autonomic Nervous System
    • Somatic Nervous System

Peripheral Nervous system (PNS)

• 12 pairs of cranial nerves
• 31 pairs of spinal nerves

PNS sends information in two directions

• Afferent Nerves: receive sensory input and send information to the CNS (direction of information is inward)
• Efferent Nerves: send motor output from the CNS (direction of information is outward)

Somatic Nervous System Vs Autonomic Nervous System

• Somatic nervous system: receives sensory information from sensory organs and controls movement of skeletal muscles
• Autonomic nervous system: regulates with smooth muscle, cardiac muscle, and glands.

Divisions of the Nervous System

• Nervous System
  • Central Nervous System
    • Brain
    • Spinal Cord
  • Peripheral Nervous System
    • Autonomic Nervous System
      • Afferent (sensory) nerves
      • Efferent (motor) nerves
      • Parasympathetic Nervous System
      • Sympathetic Nervous System
    • Somatic Nervous System
      • Afferent (sensory) nerves
      • Efferent (motor) nerves

Efferent Nerves of the Autonomic Nervous System

• PARASYMPATHETIC DIVISION
  • "Rest and Relax"
    • Constricts pupil
    • Stimulates salivation
    • Slows heart
    • Constricts breathing
    • Stimulates digestion
    • Stimulates gallbladder
    • Contracts bladder
    • Stimulates sex organs
• SYMPATHETIC DIVISION
  • "Fight, Flight, or Freeze"
    • Dilates pupil
    • Inhibits salivation
    • Accelerates heart
    • Facilitates breathing
    • Inhibits digestion
    • Stimulates release of glucose
    • Secretes epinephrine and norepinephrine
    • Relaxes bladder
    • Inhibits sex organs

Efferent Nerves of the Autonomic Nervous System

• Sympathetic Nervous System:
  • Prepares the system for intense physical activity
  • “fight or flight”
• Parasympathetic Nervous System:
  • Opposing effects
  • Slows energy functions
  • Relaxes the body
  • “rest & relax” or “rest & digest”

Anatomical directions

• Neuroaxis
• Dorsal
• Rostral or anterior
• Ventral
• Lateral
• Medial
• Caudal or posterior

Anatomical directions defined

• Neuroaxis: imaginary middle line through CNS; reference for anatomical directions
• Dorsal: back or top of brain (dorsum means back)
• Ventral: from or bottom of brain (ventrum means belly)
• Anterior or rostral: toward the front or nose/mouth
• Posterior or caudal: toward the rear or tail
• Lateral: toward side
• Medial: toward middle
• Ipsilateral: same side of body
• Contralateral: opposite side of body

Anatomical planes

• Transverse plane
• Horizontal plane
• Sagittal plane

Anatomical planes defined

• Transverse, or coronal – slice along the plane of the face; slicing like bread or salami
• Horizontal – a slice parallel to the ground
• Sagittal – a vertical slice through the middle of the face; a midsagittal section separates the left and right halves (hemispheres)

Anatomical Directions

• Ventral
• Anterior
• Posterior

Cells of the Nervous System

• Neurons
• Glial cells

Cells of the Nervous System

• Nervous system
  • Central nervous system (CNS)
    • Brain
    • Spinal cord
  • Peripheral nervous system (PNS)
    • Somatic nervous system (SNS)
      • Afferent nerves
      • Efferent nerves
    • Autonomic nervous system (ANS)
      • Afferent nerves
      • Efferent nerves
      • Sympathetic nervous system
      • Parasympathetic nervous system

Lecture Content

• Neurons
  • External & Internal features
  • Various ways of classifying neurons
• Glia
• Blood-brain barrier

Cells of the Nervous System

• Neurons
  • Specialized cells for the reception, conduction, and transmission of electrochemical signals
  • Many shapes, sizes, locations, etc
• Glial cells
  • “Nerve glue”
  • Several functions

Neurons are one of many cell types found in the body

• Types of Cells in the Body
  • Stem Cells
  • Bone Cells
  • Blood Cells
  • Muscle Cells
  • Fat Cells
  • Skin Cells
  • Nerve Cells
  • Endothelial Cells
  • Sex Cells
  • Pancreatic Cells
  • Cancer Cells

External Features of Neurons

• Cell Body (soma)
• Dendrites
• Axon Hillock
• Myelin
• Nodes of Ravier
• Terminal Button
• Axon

External Features of Neurons Defined

• Cell body (soma): The metabolic center of the neuron
• Cell membrane: The semipermeable membrane that encloses the neuron.
• Dendrites: The short processes emanating from the cell body, which receive most of the synaptic contacts from other neurons.
  • Dendritic spines
• Axon hillock: The cone-shaped region at the junction between the axon and the cell body.
• Axon: The long, narrow process that projects from the cell body.
• Myelin: The fatty insulation around many axons.
• Nodes of Ranvier: The gaps between sections of myelin.
• Buttons: The buttonlike endings of the axon branches, which release chemicals into synapses.
• Synapses: The gaps between adjacent neurons across which chemical signals are transmitted.

The Cell Membrane: Lipid Bilayer

• Lipid bilayer
• Channel protein
• Signal protein

Internal Structures of a Neuron

• Cytoplasm
• Nucleus
• Dendritic spines
• Dendrite
• Membrane
• Microtubules
• Mitochondria
• Myelin sheath

Axoplasmic Transport

• Motor proteins transport cargo in two directions along microtubules

Axoplasmic Transport

• Anterograde transport: transports cargo from the soma to the terminal button.
• Retrograde transport: carries cargo from the terminal buttons to the soma.

Inside Neurons

• Dendrites, Rough ER (Nissl body)
• Polyribosomes
• Ribosomes
• Golgi apparatus
• Nucleus
• Nucleolus
• Membrane
• Microtubule
• Mitochondrion
• Smooth ER
• Synapse (Axodendritic)
• Microtubule
• Synapse Neurofibrils
• Neurotransmitter
• Receptor
• Synaptic vesicles
• Synapse (Axoaxonic Synaptic cleft
• Axonal terminal
• Synapse (Axosomatic)
• Node of Ranvier
• Axon hillock
• Nucleus
• (Schwann cell)
• Myelin Sheath (Schwann cell)
• Dendrites
• Microfilament
• Microtubule
• Axon

Inside Neurons (cont.)

• Microtubules: structural polymers responsible for rapid transport of material throughout neurons
• Cargo Vesicles: membranes packed with organelles or other cell products.
• Synaptic vesicle: spherical membrane packages that store neurotransmitter molecules ready for release near synapses
• Neurotransmitters: molecules that are released from active neurons and influence the activity of other cells

Synapses between neurons

• Presynaptic neuron
• Postsynaptic neuron

Types of synapses between neurons

• Synapse on soma
• Soma
• Axon hillock
• Synapse on dendrite
• Axon
• Myelin sheath
• Terminal button
• *Arrows indicate direction of information flow

Unique structure enables function

• *Arrows indicate direction of information flow
• Axon hillock reception, conduction, and transmission of electrochemical signals within circuits

Classification of Neurons

• Neurons can be classified based on many features
  • Early neuroscientists used their shape and location.
  • One aspect of shape = number of processes

Classification of Neurons Based on Number of Processes

• Process refers to the number of extension off of the cell body

Classification of neurons according to shape:

• Unipolar
• Bipolar
• Multipolar
• Many beautiful shapes & sizes

Classifying Neurons Based on the Presence or Absence of Spines

• The presence of many dendritic spines makes a neuron spiny
  • Tiny protrusions from dendrites, which form functional contacts with neighboring axons of other neurons

Classifying Neurons Based on the Presence or Absence of Spines

• SPINY NEURONS
  • GLU
  • GABA
• NON-SPINY NEURONS
  • GABA

Golgi Stain a silver staining technique

Santiago Ramón y Cajal

• Father of Neuroscience
• He shared the Nobel Prize in Physiology or Medicine in 1906 with Camillo Golgi
• Neuron Doctrine

Classification of Neurons

• Number of processes
• Shape
• Location of cell body
• Neurotransmitters they release
• Receptors they express
• Other genetic markers
• Type/direction of information communicated

Three types of neurons based how information is relayed between the PNS & CNS

• Sensory: Receives sensory information from the periphery
• Interneuron: relays information between neurons
• Motor: Sends signals out to the periphery

Three types of neurons based how information is relayed between the PNS & CNS

• Sensory neuron
  • Afferent neuron
• Interneuron
• Motor neuron
  • Efferent neuron

A Nerve (PNS) is a bundle of axons

• A nerve consists of a membrane sheath encasing bundles of axons.

Cells of the Nervous System

• Neurons
  • Specialized cells for the reception, conduction, and transmission of electrochemical signals
  • Many shapes, sizes, locations, etc
• Glial cells
  • “Nerve glue”
  • Several functions

Four Types of Glial Cells

• Astrocyte
• Microglia
• Oligodendrocyte
• Schwann cell

Glial cell: Astrocyte functions

• Provide physical support to neurons
• Wrap around blood vessels to
  • Provide nourishment to neurons (glucose transporters)
• Control chemical composition of fluid surrounding neurons (Blood- Brain Barrier)
• Clean up debris & form scar tissue

Glial cell: Microglia functions

• Involved in response to injury or disease
• They respond to injury (like traumatic brain injury) with inflammatory response

Glial cells that produce myelin (and speed up signal conduction):

• Oligodendrocytes & Schwann cells

Differences between myelin in CNS & PNS

• CNS: Oligodendrocyte
• PNS: Schwann Cell
• Different chemical composition and function
• Oligodendrocytes surround many axons, while Schwann cells surround a single portion of one axon
• Schwann cells help facilitate nerve growth (axon regeneration) in the PNS after injury, while Oligodendrocytes do not in the CNS

Myelin is an extension of the cell membrane of both types of glial cells

• CNS Myelin: Oligodendrocyte
• PNS Myelin: Schwann Cell

Multiple Sclerosis

• Autoimmune system attacks myelin in the CNS
• Multiple sclerosis causes many different symptoms, including vision loss, pain, fatigue, and impaired coordination

Blood-brain barrier

• A term used to describe the unique, heavily-restrictive properties of the blood vessel of the CNS
• Capillaries of the brain form a tight-knit cellular barrier that does not allow for the free movement of many substances into neural tissue

Blood-brain barrier

• A term used to describe the unique, heavily-restrictive properties of the blood vessel of the CNS
• Blood vessels can convey helpful ( oxygen, nutrients, etc.) and unhelpful substances (toxin, pathogens, etc.)
• Capillaries of the brain form a tight-knit cellular barrier that does not allow for the free movement of many substances into neural tissue
• Astrocytes help support & maintain this cellular barrier

Blood brain barrier

• Very selectively permeable
• Only tiny, water-soluble substances can diffuse through gaps
• Some fat-soluble substances can pass through cell membranes
• Others must be actively transported
• Function:
  • Regulate the composition of the extracellular fluid
  • Preventing chemicals from acting on neurons
  • Weak areas allow brain to stimulate vomiting in response to toxins

Blood-CSF barrier

• Fluids of the CNS:
  • CSF
  • Extracellular fluid: fluid around the neurons & glial cells

Lecture Content

• Neuroanatomical Techniques
• Neural development

Neuroanatomical Techniques

• Golgi stain
• Nissl stain
• Immunohistochemistry
• Neuroanatomical tracing
  • Retrograde
  • Anterograde

Staining

• Cut tissue into slices along the anatomical plane of interest
• Soak or wash in the staining solution(s)
• Mount them on microscope slides

Golgi Stain: study of individual neurons

Nissl Stain highlights cell bodies of all neurons; allowed estimation of cell density in tissue.

• Helps distinguish Gray matter from white matter

Immunohistochemistry (IHC) helps visualize cells based on the proteins they express

• Uses modified antibodies to add a visible compound to neurons of interest (ie. neurons that release a certain neurotransmitter)
• Slices in well-plate Slices soaked in Primary antibody Slices soaked in Secondary antibody with visible element

Immunohistochemistry (IHC) helps visualize cells based on the proteins they express

• Uses modified antibodies to add a visible compund to neurons of interest (ie. neurons that release a certain neurotransmitter)

Immunohistochemistry (IHC) helps visualize cells based on the proteins they express

• Uses modified antibodies to add a visible compound to neurons of interest (ie. neurons that release a certain neurotransmitter)
• Colored chemical reaction compound = visible with brightfield microscope Fluorescent dye = visible with fluorescence microscope

Neuroanatomical Tracing helps visualize cells based on their relative location (cell bodies & projections)

• Conducted in intact brains with injection of fluorescent dye into specific sites
  • Anterograde: from the soma to the terminal button.
  • Retrograde: from the terminal buttons to the soma

Neuroanatomical Tracing cont. (example)

• Inject a combo of an Anterograde Tracer and a Retrograde Tracer into Area A
• Visualize the location of cells projecting from A to B as well as cells projecting from B to A

How do cells develop and find their targets?

• Developing epidermis
• Neural tube
• Developing spinal ganglion

Phases of Development

• Creation of neural tube
• Neural proliferation
• Neural migration
• Axon growth and synapse formation
• Neuron death and synapse refinement

1. Creation of the Neural Tube

2. Neural Proliferation: cells multiply and form three swellings

• Forebrain
• Midbrain
• Hindbrain
• Telencephalon
• Mesencephalon
• Metencephalon
• Myelencephalon

3. Neural Migration

• Once cells have proliferated, they migrate (move) to their final destinations to form structures and brain areas.
• Migrating cells are immature, lacking axons and dendrites
• Migrating cells move in two directions by two different means
• Cortical layers form in an “inside out pattern”

Two directions of neural migration

• Tangential migration
• Radial migration

Two methods of migration

• Somal Translocation (Radial or Tangential)
• Glia-Mediated Migration (Radial Only)

Inside out development of cortical layers

• Process is supported by an early progenitor cell called a radial glial cell
• Note: Numbers indicate order of layer development NOT anatomical reference

Inside out development of cortical layers

• Meninges
• Marginal zone
• Cortical plate
• Subplate
• Intermediate zone
• Subventricular zone
• Ventricular zone

Phases of Development

• Creation of neural tube
• Neural proliferation
• Neural migration
• Axon growth and synapse formation
• Neuron death and synapse refinement

4. Axon growth and synapse formation

• At the growing tip of each axon, the growth cone extends and retracts as if exploring to find its way

Phases of Development

• Creation of neural tube
• Neural proliferation
• Neural migration
• Axon growth and synapse formation
• Neuron death and synapse refinement

Neuron Death and Synapse Refinement

• Overproduction: during development many neurons die.
  • programmed cell death (Apoptosis)
    • (differs from necrosis, which is unprogrammed form of cell death that occurs in response to overwhelming chemical or physical insult)
• Neurons die due to failure to find synaptic partners and compete for neurotrophic factors provided by targets (e.g., NGF, nerve growth factor)

Neuron Death and Synapse Refinement (cont.)

• Axons are fine-tuning connections, forming and reforming connections
• Synapse refinement is likely influenced by chemical signals and by spontaneous and experience-evoked neural activity

Synapse rearrangement and refinement

• A diffuse pattern of synaptic contact is characteristic of early stages of development.
• A more focused pattern of synaptic contact is present after synapse rearrangement.

Refining Neural Connections: Overproduction and Pruning

• Experience shapes brain architecture by early overproduction of neurons, followed by later apoptosis and refinement of synaptic connections based on learning and exposure to stimuli.

Refining Neural Connections: Overproduction and Pruning

• Brain development begins during the prenatal period and extends through adulthood.
• Note: new synapses can form in adulthood. This development phase (synaptogenesis) is referring to the first synaptic connections

Postnatal Brain Development

• Brain development continues after an animal is born
• The human brain continues to develop for at least two decades
• Then even after that, the adult brain continues to undergo subtle changes throughout life
• Experience affects brain development and maturation

Examples of how experience affects brain function in developing and adult brains

• Development:
  • If crossed eyes are not corrected during development (1-3 years), depth perception may be irrevocably impaired
  • “use it or loose it”
• Adulthood:
  • Individuals who learn braille will have a larger portion of sensory area of their brain that respond to finger sensation.

Neurogenesis

• The process by which new neurons are formed in the brain
• Once thought to stop in adulthood
• Now, we know new neurons are formed in (at least) two brain areas

Neurogenesis in the adult human hippocampus

The developing brain is vulnerable

• More than 200 genetic mutations associated with developmental disability
• Developing brain is more vulnerable than the mature brain to malnutrition, toxic chemicals and infections.
• Examples:
  • Fetal alcohol syndrome: Dendrites tend to be short, with few branches (toxin)
  • Rett Syndrome: Anomaly of brain development with developmental disability affecting mainly girls older than 1-2 years. Associated with lack of dendritic development. (genetic mutation)
  • Phenylketonuria (PKU): lack enzyme to convert protein phenylalanine to tyrosine. If consume food with phenylalanine, it accumulates in the blood and interferes with myelination. (metabolic disorder)

Some developed brains also experience damage at the cellular level

• Parkinson’s disease: degeneration of pigmented cells in the midbrain

Some developed brains also experience damage at the cellular level

• Alzheimer’s disease: buildup of protein aggregates outside of cells (beta-amyloid plaques) and inside cells (tau tangles)