cerebral hemispheres are absent 

and replaced by fluid-filled cysts

•  Diagnosis is commonly post-natal, 

but with advancements in imaging, 

it can also be detected prenatally 

•  Causes unknown, but thought to 

be linked to infection or trauma 

during early embryonic 

development 

•  Results in paralysis, blindness, 

respiratory problems, spasticity, 

seizures, problems with feeding, 

impaired physical and mental 

development 

•  Many children die before age 1 

(down syndrome) – delayed 

neurodevelopment and mental retardation 

Extra chromosome 21. Diagnostic maternal 

blood test for chromosome 21 is common

Pediatric Autoimmune 

Neuropsychiatric Disorders associated with 

Streptococcal infection) – obsessive 

compulsive disorder (OCD)? 

Inappropriate severe immune reaction to 

bacterial infection 

led to 

advances in neurotrauma research and may one day lead 

to a therapy for spinal cord and brain injury. 

- they are a disease 

- ementia = getting old. losing memory. sth irreversible. but if u call it a "disease" there may be a cure. 

- alzheimer ( a type of dementia): a disease that may be cured....

of or relating to the nervous system. For example, neural cells can 

be neurons or glia. 

refers to neurons specifically (not glia). Neurons are often very 

polarized cells with a cell body (soma), dendrites, and a projection axon. 

Neurons are electrically excitable cells that process and transmit elements 

of behavior rapidly. They connect to other cells via electrical and chemical 

synapses. 

There are likely thousands of different neuronal phenotypes, but they all 

technically fall within 3 types of location: 

•  Sensory (afferent) neurons - originate outside the central nervous system 

(CNS) and terminate within the CNS. 

•  Motor (efferent) neurons (or motorneurons) - originate in the CNS and 

terminate outside the CNS. 

•  Interneurons - originate and terminate within the CNS (and are the 

majority of CNS neurons).

refers to glial cells are non-neuronal cells that maintain CNS 

homeostasis, form myelin, and provide support and protection for neurons. 

There are several different types of glia, including: 

•  Microglia are specialized macrophages of the CNS and can phagocytize 

other cells. They are highly reactive to any CNS injury or inflammation 

•  Macrogliaare larger glial cells and come in a number of types: 

•  oligodendrocytes (within the CNS) or Schwann cells in the peripheral 

nervous system (PNS) are the main myelinatingglial cells 

•  astrocytes (CNS) are the most abundant type of glial cell and 

regulate the extracellular CNS environment by removing excess ions, 

notably potassium, and recycling neurotransmitters released during 

synaptic transmission. They are sensitive to CNS injury or 

inflammation 

•  ependymal cells line the wall of the ventricles and produce 

cerebrospinal fluid (CSF). They are also thought to act as CNS stem 

cells 

•  satellite glial cells are small cells that surround neurons in sensory, 

sympathetic and parasympathetic ganglia of the PNS and have 

similar properties to astrocytes (see above) 

a bundle of peripheral axons that transmits sensory or 

motor information are called nerves. bundles of axons projecting through the 

CNS are called tracts (or pathways) 

has two meanings in the nervous system. Can either refer to the 

nucleus of a specific cell or a collection of functionally-related neuronal cell 

bodies. 

A collection of functionally-related neuronal cell bodies that 

resides in the peripheral nervous system. Ganglion is the peripheral 

equivalent of nucleus.

Nervous system 

peripheral      central ns

Peripheral = somatic and autonomic ns 

Central ns = brain and spinal cord

somatic = motor nerves and sensory ganglia

autonomic = sympathetic and parasympathetic. 

1. Cerebellum: motor control 

2. Midbrain: vision, hearing, voluntary movement 

3. Pons: relay center for all types of information 

(motor, sensory, and autonomic) 

4. Medulla: vital functions (e.g. breathing, heart 

rate) 

7. Thalamus: sensory relay to cortex 

8. Hypothalamus: autonomic regulatory center 

(e.g. body temperature, appetite) 

9. Frontal lobeof cerebral cortex: fine 

movements, higher cognitive functions 

10. Parietal lobeof cerebral cortex: perception, 

spatial orientation 

11. Occipital lobeof cerebral cortex: vision 

12. Temporal lobeof cerebral cortex: auditory 

function & language processing 

13. Limbic lobeof cerebral cortex (including 

hippocampus & amygdala) : emotional responses 1. 

Define these anatomical positions. 

Dorsal 

ventral 

cranial/cephalic/rostral

caudal

anterior

posterior

medial 

lateral 

proximal 

distal 

Dorsal: toward the back (see also ‘posterior’) 

Ventral: toward the belly (see also ‘anterior’) 

Cranial/cephalic/rostral: toward the head (rostral actually means 

“toward the beak”, but is frequently used for all vertebrates)

Caudal: toward the tail 

Anterior: toward the front (important when an animal – or an embryo – 

does not have a head) 

Posterior: toward the back 

Medial: toward the midline 

Lateral: away from the midline; positions on appendages (fins or limbs) 

are described using proximal and distal: 

Proximal: toward the point of attachment (to the body)

Distal: away from the point of attachment 

Transverseplane (also called a cross-section) divides the fish into cranial 

and caudal halves 

•  Frontalplane (also called a longitudinal section) divides the fish into dorsal 

and ventral halves 

•  Sagittalplane (also called sagittal section) divides the fish into left and right 

halves (if the section is made at the midline, it is called midsagittal; if the 

section is made away from the midline, it is called parasagittal) 

1. Mouse 

2. Chicken 

3. Frog 

4. Zebrafish 

5. Fly 

6. Nematode 

zebra fish is the weakest (relatively new model) 

- has not provided much insights

Strongest is the fly and mouse. 

mouse is stronger because its a mammal and great genetic tool. 

the problem with mice is that they are either alive or dead

- rats can be trained but mice cant. Rats good for studying behaviour but mice cant. 

before it was mostly done in developing chicks and frogs. 

Similar to humans: 

• Embryonic morphology 

• Organization of the adult central nervous 

system (CNS) 

• Genomic manipulations (e.g. gene knockout, 

gene knockin, Cre/lox)

mice has lots of genetic manipulation 

 - able to knock out genes at multiple sites and track them 

Exploit Cre-lox system and fluorescent proteins to generate mice in which 

neurons and glia can be identified with specific colors of varying hue. 

Chick: 

• accessible embryos well-suited 

to surgical manipulations (e.g. 

Hasan SJ, Keirstead HS, Muir GD, 

Steeves JD. 1993. Axonal regeneration 

contributes to repair of brainstem-spinal 

neurons in embryonic chick. Journal of 

Neuroscience13(2): 492-507. 

• tissue removal and 

transplantation studies 

- simple vertebrates

-transparent embryo

they are transparent. 

once can see the developing embro

- but they are rather fragile after manipulation of their gene. They die as consequence. 

Adult CNS consists of a brain and 

segmented ventral nerve cord

The adult C. elegansnervous system is simple: 302 neurons and 56 glia 

- have very specific nervous system

1.  Where is your protein/RNA expressed? 

2.  What does your protein do? 

3.  Which cellular interactions are involved, 

necessary or sufficient for function? 

In situ hybridization (ISH) 

•  used to detect presence of mRNA of interest 

•  oligonucleotide (RNA or DNA) linked to 

radioactive or fluorescent label for detection 

•  wide range of applications; high sensitivity 

Reverse transcription polymerase chain reaction (RT-PCR) 

•  is a technique used to amplify RNA and quantify amount of RNA 

in a sample 

•  first, the enzyme reverse transcriptase transcribes RNA into 

DNA 

•  the DNA of interest is then amplified using PCR (Fig. 2) 

§  DNA polymerase makes more copies 

•  can quantify amount of RNA in a single cell! 

Northern blot 

•  used to detect amount/size/variants of 

transcript of interest 

•  first run the sample on agarose or 

polyacrylamide gel 

•  then probe gel using RNA or DNA 

hybridization probe (Fig. 3) 

- protein expression

•  is the detection of antigens (specific bits of protein) in tissue using 

antibodies attached to fluorescent probes 

•  can establish spatio-temporal localization of proteins of interest 

Immunocytochemistry (ICC)

•  is the detection of antigens in cultured cellsusing antibodies 

•  establish whether a cell type expresses a specific protein 

•  very similar to Northern blot, but assays for protein expression 

using an antibody 

2) Determining the function of a protein 

lof and gof experiments are powerful, and are usually paired. 

i) Loss-of-function (lof) experiments 

General question: Is protein X requiredfor process Y to occur?

Knockout animals

Purpose: remove functional gene in the gemone; characterize 

differences in phenotypes during development/in adult 

•  add engineered sequence to isolated mouse embryonic stem 

cells (from morula) by electroporation (shock) 

•  inject these cells into blastulae, then implant in uterus of a mouse 

•  select for embryos that have the knockout gene in germline 

•  causes a permanent change in that individual’s genome (all 

cells)

RNA interference (RNAi)

Purpose: silencegene expression by addition of double-stranded 

small-interfering (si)RNA 

•  after introduction into a cell, siRNA is cut into bits by an enzyme 

•  these shorter dsRNA strands are incorporated into a protein 

complex, where complementary sequences (i.e. target mRNA) 

are bound and degraded 

•  inhibition is inducible and reversible, and can be introduced in 

discrete groups of cells. Inhibition may not be complete 

•  other forms of gene silencing (similar principles): antisense RNA 

(single strand) and morpholinos (synthetic nucleic acids; Fig. 8) 

Dominant negative 

•  Introduction of a mutated protein that interferes/prevents the 

normal function of the wild-type protein in a cell 

•  e.g. for a protein that usually functions as a dimer – a mutation in 

the catalytic, but not dimerization domain inhibits protein function 

what is the Cre/loxsystem

Purpose: remove (or add) genes from specific cell types or tissues 

at a certain developmental stage 

•  gene of interest is flanked by loxPsites (in all cells) – these act 

as recognition sites for the enzyme Cre 

•  Cre recombinase is an enzyme that recombines DNA at these 

loxPsites. Thus, Cre cuts out DNA that resides between loxP

sites and stitches the remaining DNA back together 

•  placing the Cregene under the control of a cell-specific promoter 

means that the gene of interest will only be removed from cells 

that express the gene with that promoter

2. Assaying for protein function 

i.  Loss-of-function experiments 

ii.  Gain-of-function experiments 

iii.  Transplant experiments 

paired experiments 

very instrumental - tell how nervous system are put together. hard to argue against for either if they are paired. 

the notochord is required for floorplateand motoneuron

development in the chick neural tube (àspinal cord). 

What would happen if you removed the notochord?if take away notochord, specialization goes away. 

 loss of function exp. 

Another gain-of-function experiment: 

additional notochord (from another animal), transplanted 

ectopically, is sufficient to direct floorplateand motoneuron

development. add notochord in the wrong position in the lateral position. 

the notochord influence development of tissue it is adjacent to. 

Used to define organization of axonal projections 

and possible neuronal connections in the 

developing or adult nervous system 

Two types: 

1. Anterograde

§  label neurons at cell bodies, look for presence of tracer in axons to 

determine axonal trajectory and axon termination 

2. Retrograde 

§  label axons within terminal fields of at specific point along axonal 

tract, look for cell bodies that contain tracer