Neuro Quiz 1

What years were declared the “Decade of the Brain”?

1990-2000

Enhance public awareness of the benefits of brain research

Presidential Proclamation: George H. W. Bush on July 17,1990

BRAIN Initiative - What does it stand for, when, funding, purpose

Brain Research through Advancing Innovative Neurotechnologies

April 2, 2013

$100 million - initial stated funding level

→ purpose: revolutionize understanding of human brain by accelerating the development and application of innovative technologies to improve treatment, prevention, and cures for brain disorders

Example: mouse and human brain cell atlases

What 2 broad tasks - demonstrate complexity of nervous system and tennis?

Sensing and movement control

What does the visual cortex do during the phase of catching / hitting the ball?

Judging the ball

What does the PREMOTOR CORTEX do during the recognition phase - tennis?

Develops a motor program

What role does the AMYGDALA play in the recognition phase - tennis?

Influences heart rate and respiration

What structures execute movement during the movement phase - tennis?

Motor cortex and basal ganglia

What structure fine-tunes movement - tennis?

Cerebellum

Major point of the Einstein example

Cognitive functions involve several cortical areas

What differences were reported between Einstein’s brain and other brains?

• Above average # of GLIAL cells

• Possibly MISSING the PARIETAL OPERCULUM

• Parietal lobe - 15% wider than normal

• Incomplete SYLVIAN FISSURE

What function was associated with the englarged parietal lobe - Einstein slide?

Mathematical reasoning

What is the other name for the SYLVIAN FISSURE?

Lateral sulcus

What is the parietal operculum associated with?

Secondary somatosensory complex

Approx. how many NEURONS are in the human brain?

10^11 neurons

Approx. how many NEURONAL CONNECTIONS are in the human brain?

10^14

Two major methods - create high-resolution mouse brain cell atlas described on the slide?

Single-cell RNA sequencing and MERFISH

*MERFISH= multiplexed error-robust fluorescence in situ hybridization

What neurological disorder listed has the greatest # of US cases?

Chronic pain - 100 million cases

$300 billion

Highest annual economic cost disorder

Alzheimer’s disease - $780 billion / year

About 7.2 million cases

Two main cell types in the nervous system

Neurons and Glial cells

Primary function of NEURONS

Signaling / Communication

Primary role of GLIAL CELLS

Maintenance and Support

What functions can the nervous system control?

Simple reflexes to complex functions including…

-Vision

-Hearing

-Speaking

-Thinking

-Learning

-Emotions

Main Signaling Unit of the Nervous System

The Neuron

Do neurons contain the same basic organelles as other cells?

Yes, but they are highly specialized for intercellular communication.

What does neuronal polarization mean?

Different parts are structurally and functionally different, it does NOT mean electrical charge.

Are mature neurons generally MIOTIC?

NO, mature neurons are POSTmiotic and can live for many years

What are the basic visible parts of a typical neuron?

Cell body/soma, dendrites, axon, pre-synaptic terminal

What are the 4 morphologically and functionally defined regions of a typical neuron?

1. Cell body (nucleus, ER, Golgi)

2. Dendrites (receive information)

3. Axon (conducts information)

4. Pre-synaptic neuron (conversion of electrical to chemical signal)

*NEURONS ARE POLARIZED CELLS

Primary function of DENDRITES

Receive information

Primary function of the AXON

Conduction / conduct information

What happens at the pre-synaptic terminal?

Electrical signal is converted to a chemical signal

What are the 3 components of a SYNAPSE?

1. Presynaptic terminal

2. Synaptic cleft

3. Postsynaptic membrane

Average # of NEURONS in the human brain

100 billion, chain of 600 miles

Ramon y Cajal

“Father of Neuroscience”

-Used silver staining to show neurons are single cells (dont form a syncytium)

Top 4 Major Ramon y Cajal discoveries:

1) Neuron Doctrine - single unit is a distinct cell

2) Principle of Polarization - signal travels in one direction

3) Principle of connectional specificity

4) Neurons have Distinct Shapes - concept of synapse; Cajal identified the GROWTH CONE for the first time

Neurons are…

Extremely polarized, very asymmetrical cells, with fine long processes

Shapes of Neurons:

Unipolar, Bipolar, Pseudo-Unipolar, Multipolar

What does the shape of Neurons reflect?

More elaborate branching of the dendritic branches = the more complex functions are mediated by the neuron

→ PURKINJE CELL (cerebellum)

Techniques - Identifying Neurons and Connections

1. Golgi Silver Staining

2. Injection - fluorescent markers (Lucifer yellow, fluorescent dextran)

3. GFP expression

4. Labeling specific neurons - immunocytochemistry

Functional Classification of Neurons

1. Sensory - receivers of information from periphery

2. Motor - senders of information to periphery

3. Interneurons - make up the bulk of the brain

A) projection neurons: long axons, connect to parts far away

B) local neurons: short axons, connect close to brain

4 Signaling Components of Neurons

1. Input Component = dendrites, cell body

2. Trigger Component = axon hillock, action potential (beginning)

3. Conduction Component = axon

4. Output Component = pre-synaptic terminal, most synapses

Stimulus INTENSITY determines…

FREQUENCY of action potentials

Increased intensity = faster (more frequent) APs

Stimulus DURATION determines…

The NUMBER of action potentials

Increased duration = increased # of APs

Electrical signals are used for

LONG distances (along the neuron)

CHEMICAL signals (transmitters) are used for…

SHORT distances (between neurons)

Universality of electrical signaling

The nature of electrical signals is identical among different neurons and among species

Information specificity of electrical signals

It is given by the connection and the transmitter type

The basic mechanism of signaling is…

The SAME in all neurons

Where do neurons differ?

At the MOLECULAR level (ion channels, receptors, transmitters)

The specificity of information (visual, pain, motor) is given by…

Specific circuitry along which the signal travels

Glial Cell Functions

1) Development: acts as GUIDES for migrating neurons and axons

-Radial glial cell

2) Maintenance: homeostasis, regulation of the blood brain barrier (BBB)

-Astrocytes

3) Structural Support (Glue)

-Astrocytes

4) Providing Nutrients to Neurons

-Astrocytes (CNS), Schwann Cells (PNS)

5) Immune Function: removing debris

-Microglia

6) Myelination: insulation of axon

-Oligodendrocyte (CNS), Schwann Cell (PNS)

7) Production of Growth: factors and GCM

-Astrocytes

8) Secretion of Cerebralspinal fluid (CSF)

-Ependymal cell

Microglia - CNS only

Act as macrophages (immune defense cells), remove neuronal debris after injury, infection, disease via PHAGOCYTOSIS

• Activated by multiple sclerosis, Parkinson’s, Alzheimer’s

Astrocytes

Astrology → keeps everything in check → homeostasis

-most ABUNDANT glial cell type in the CNS

-GFAP is an astrocyte protein marker

-Structural support

-Control chemical environment via spatial buffering → highly permeable to K+

-Supply neurons with nutrients (lactate from glycogen)

-Glial end feet: regulate development of BBB

-do not have direct connections with neurons, form gap junctions among themselves

Astrocytes - Glutamate-Glutamine Cycle

Recycles Glutamate at the synapse

-Glutamine synthetase converts glutamate → glutamine

-Glutamine is released and taken back up by the pre-synaptic neuron, where glutaminase converts glutamine → glutamate for reuse.

*This process happens in the astrocyte

Oligodendrocytes

-Mostly in white matter

-Insulates axons with myelin in CNS, one oligodendrocyte can wrap several axons

Myelin Difference

Myelin in Oligodendrocytes DOES NOT = Myelin in Schwann Cells

→ they have different composition

Radial Glia

Development and Positioning

→ postmiotic neurons migrate to the appropriate layer along radial glial cells during development

Schwann Cells

Insulate axons with myelin in the PNS, 1:1 ratio of Schwann cell to axon

-Non-Myelinated spaces are the Nodes of Ranvier → sodium channels are highly concentrated (action potential jumps from one to another)

Key Features of Fast and Directional Signaling - Neurons

1. Electrical Excitability

2. Polarization (polarity)

What organisms are used to study cell polarity typically?

Drosophilia, C. Elegans, Yeast

Establishment of Polarity in Hippocampal Neurons:

Lamellipodia → Immature neurites → axon formation → dendrite formation → further maturation

Neuronal Polarity - how is it established and maintained?

1. Selective Delivery of Protein: need voltage gated/activated ion channel protein channels, need neurotransmitter receptor proteins

2. Selective Fusion of Membranes: SNARE proteins = mediate vesicle fusion with plasma membrane

3. Selective Retention of Proteins: diffusion barrier of axon initial segment restricts unwanted mixing of membrane potential

Differences between Axon and Dendrites

AXON:

-1 axon

-Generally long

-Intital segment

-Can be myelinated

-Na+/K+ channels

-Not all organelles

-tau

DENDRITE:

-Less than or equal to 1 dendrite

-Generally shorter, branched

-Continuous w/ cell body

-Not myelinated

-Neurotransmitter receptors

-Most organelles

-Map 2

Plasma Membrane Components - Neuron

• Asymmetric Lipid Bilayer w/ Proteins

• Hydrophobic Barrier Impermeable to Most Water-Soluable Molecules

*Very important for maintains specific intra and extra cellular concentrations of ions, metabolites, and transmitters → due to pumps, transporters, channels

Cytosol - Neuron

Consists soluble proteins, enzymes with metabolic functions, signaling proteins concentrated in the cytoskeletal-membrane interface

Cytoskeleton - Neuron

Function - cell division, shape determination, motility, organelle transport

Contains micotubules, actin filaments, neurofilaments

Accounts for 25% of the neuronal protein, tubules makes up 10% of total brain protein

Microtubules (MTs)

Made of Alpha and Beta Dimers

Plus ends toward the Beta subunit

GTP or GDP Binding for B tubulin, GTP binding for A tubulin

-Rapid changes of growing / shrinking regulated by free dimer concentration, rate of GTP hydrolysis, MT associated proteins

-GTP cap favors microtubule growth

-MAPs can stabilize MTs, marker proteins

→ tau is axonal marker

→ MAP2 is specfic to dendrites

Growing Microtubule is…

Rate of subunit addition EXCEEDS rate of GTP hydrolysis

Shrinking Microtubule =

Rate of GTP hydrolysis EXCEEDS rate of subunit addition

Microtubule Function in Neurons

-Axonal growth and balance

-Provide tracks for long-range protein and organelle transport

-Kinesin motors: mediate either plus or minus end oriented transport

-Dynein motors: minus end oriented transport

Microtubule polarity in neurons

Axons: all MT plus ends are oriented towards growth cone

Dendrites: mixed MT polarity in higher organisms (vertebrates)

F-Actin

-Very conserved and abundant

-Two parallel protofilaments made from a globular monomer, forms a right handed helix

-Plus end is the growing end

-ATP/ADP binding

F-Actin Functions in Neurons

Structural support, growth cone motility and guidance

F-Actin Dynamics

-Free monomer concentration and actin associated proteins

ATP-Bound → ASSEMBLE ACTIN

ADP-Bound → DISASSEMBLE ACTIN

Neurofilaments

-Tetramer is an organizing unit, fiber is not polarized

-Most abundant fibrillation components in axon that provide strength

-Dont have a plus or minus end, not as dynamic

Where is genetic information stored in neurons?

Nucleus, some in mitochondria (mito tRNA, mito rRNA, a few mito proteins)

Where does transcription and RNA processing occur?

Nucleus

Where does translation occur?

In the cell body and dendrites

→ there is also evidence for protein synthesis in the axon and nerve endings

Cytosolic proteins are translated …

On free ribosomes

Secretory and membrane proteins are synthesized by…

Ribosomes bound to the rough ER (RER)

Proteins with special destinations have…

Signal sequences

→ mitochondria, nucleus, peroxisomes, ER

→ the classic ER retention signal is the C-terminal KDEL sequence

What are the post-translational modifications?

1) Glycosylation

2) Phosphorylation / Dephosphorylation

3) N -acylation

4) Isoprenylation

5) Ubiquitination

Glycosylation

Attaching a sugar, carbohydrate modification

→ important for outer membrane proteins for molecular recognition

→ N-linked, O-linked

Phosphorylation / Dephosphorylation

Kinases, Phosphatases

→ affects signal transduction, protein function/activity

N-acylation

Attached carbon chain to protein

→ membrane association

→ can be diff lengths

Isoprenylation

Membrane association

→ prenyl-group

→ Ras-GTPase

Ubiquitination

Ubiquitin → 76 a.a.

→ protein degradation

→ proteasome

2 major functions of the Golgi Complex

1) Modifications of proteins: Glycosylation and Phosphorylation

2) Sorting and targeting of proteins into different vesicles

Why is ENDOCYTOSIS important in neurons?

1) Recycling of synaptic vesicles (membrane)

2) Keeping the neuron at the same size

3) Regulation of the amount of membrane receptors

*Clathrin mediates endocytosis

Proteins and Axonal transport

Most proteins are synthesized in the cell body → need to be transported along the axon

-Paul Weiss tied off sciatic nerve

-Radioactive labeling of neuronal proteins

-Video enhanced DIC light microscopy

-Fluorescent labeling techniques combined with photobleaching and photoactivation

Kinesin moves…

Minus end to Plus end (anterograde)

Dynein moves…

Plus end to Minus end (retrograde)

Central Nervous System is composed of…

Brain, Spinal Cord

Peripheral Nervous System (PNS) is composed of…

Somatic Division (Sensory neurons) and Autonomic division (motor)

Parasympathetic

Rest and Digest

Sympathetic

Fight or Flight

Cephalic Flexure

Remains after development causing the tilt between forebrain and spinal cord axes

Spinal Cord

• Processes sensory information from limbs and trunk and many internal organs

• Controls body movements

• Transmits sensory information in ascending tracts and motor information in descending tracts

Amount of Segments (spinal cord)

Cervical = 8

Thoracic = 12

Lumbar = 5

Sacral = 5

White matter is most abundant…

At the cervical level

→ more ascending and descending axons