FROM MOLECULE
TO MIND
(Synapse biology, Neurophysiology, Cell
biology & Neurobiology, Methods & Models)
Master Biomedical Sciences –
Neurobiology
Claire Snel, Year 1, 2024
,Table of contents
Neuroanatomy ............................................................................................................................. 2
Lecture 1 – Neuroanatomy 1 ............................................................................................................. 2
Synapse biology ........................................................................................................................... 9
Lecture 1 – Introduction and synapse probability ............................................................................... 9
Introduction ................................................................................................................................. 9
Synapse probability .................................................................................................................... 10
Lecture 2 – Postsynaptic organization ..............................................................................................14
Lecture 3 – Synapse biology 3 ..........................................................................................................19
Lecture 4/5 – Functional Genomics of the synapse ...........................................................................20
Neurophysiology ......................................................................................................................... 26
Lecture 1 – Book Neuroscience Purves chapter 2-4 ..........................................................................26
Ion channels .............................................................................................................................. 26
Resting membrane potential ....................................................................................................... 30
Active properties of neurons ....................................................................................................... 33
Action potential propagation ...................................................................................................... 36
Lecture 2 – Cortical organization & human mental ability (Purves chapter 27) ....................................40
Lecture 3 – Optogenetics ................................................................................................................45
Lecture 4 – Synaptic plasticity (Purves chapter 8 & 30) ......................................................................55
Paper 1 – Navabi et al., 2014 Nature – Engineering a memory with LTD and LTP...................................61
Lecture 5 – Memory (Purves chapter 30)...........................................................................................67
Paper 2 – Liu et al., 2012 Nature – Optogenetic stimulation of hippocampal engram activates fear
memory recall ................................................................................................................................72
Basics in cell biology and Neurobiology ........................................................................................ 80
Lecture 1 – Intracellular compartments and transport (ECB chapter 15) ............................................80
Lecture 2 – Intracellular signaling (ECB chapter 16 & Purves chapter 7)..............................................87
Lecture 3 – Protein structure and function (ECB chapter 4) ................................................................96
Lecture 4 – Cytoskeleton (ECB chapter 17) ..................................................................................... 101
Lecture 5 – DNA and chromosome (ECB chapter 5) ........................................................................ 106
Lecture 6 – From DNA to Protein: How cells read the genome (ECB chapter 7) ................................. 110
Lecture 7 – Synapses (Purves chapter 5) ........................................................................................ 115
Lecture 8 – Neurotransmitters and their receptors (Purves chapter 6) .............................................. 121
Lecture 9 – Synaptic plasticity (Purves chapter 8) ........................................................................... 127
Methods and models in neuroscience ........................................................................................ 133
Lecture 1 – C. elegans ................................................................................................................... 133
Lecture 2 – Yeast .......................................................................................................................... 141
Lecture 3 – Drosophila .................................................................................................................. 145
Lecture 4 – Mutant mice ................................................................................................................ 149
1
,Neuroanatomy
Lecture 1 – Neuroanatomy 1
Where it al starts – brain development
- From neural plate to neural tube
Neural tube expansions
1. Cephalic flexure
2. Cervical flexure
3. Pontine flexure
Embryonic to adult brain development
- Neural tube grows into the brain vesicles
o Prosencephalon
§ Telecenphalon
§ Diecephalon
o Mesencephalon
§ Mesencephalon
o Rhombencephalon
§ Pons
§ Cerebellum
§ Medulla oblongata
Saggital brain section of an adult still represents the embryonic
neural tube expansions
- Telencephalon is largest part of the brain, whole cortex and basal
ganglia
- Diencephalon is the wall of the ventricle
- Mesencephalon and metencephalon giving rise to the brainstem
- Myelencephalon giving rise to brain stem and spinal cord
Anatomical directions
• Anterior: In front of; toward the face
• Posterior: Behind; toward the back
• Superior: Above; toward the head
• Inferior: Below; toward the feet
• Medial: Toward the middle
• Lateral: Toward the edge
• Dorsal: Toward the top of the brain or the back of the spinal cord
• Ventral: Toward the bottom of the brain or the front of the spinal cord
• Rostral: Toward the front of the brain or the top of the spinal cord
• Caudal: Toward the back of the brain or the bottom of the spinal cord
2
,Anatomical sectioning
- Horizontal/axial – you can see the brain from the top
- Coronal/ frontal – you look into the front of the brain
- Saggital – you can see the middle of the brain (medial/ lateral)
Functional neuroanatomy – The brain’s major white matter tracts
Myelin
Ø Myelin is a major component of white matter of the brain
o White matter is found in the deeper tissues of the brain
(subcortical)
§ It contains nerve fibers (axons), which are extensions of
nerve cells (neurons)
§ Many of these nerve fibers are surrounded by a type of
sheath or covering called myelin
Ø Electro micrograph of rat prefrontal cortex
o Dark rings are myelin membranes, surround neuronal axons
o Myelin is important for speeding up the conduction velocity/ speed of action
potentials
o Myelin is produced by oligodendrocytes (which are glial cells)
§ Glial cells: any of the cells that hold nerve cells in place and help them
work the way they should
• The types of glial cells include oligodendrocytes, astrocytes,
microglia, and ependymal cells > also called neuroglia
Oligodendrocyte precursor cells (OPSc)
- These oligodendrocytes arise from OPScs, these are also
present in adult brains (all throughout the brain)
- When you have brain injury, lesion in myelin > these cells
can di]erentiate/ proliferate and repair the damage >
plastic population of cells
Myelin and oligodendroglia in health and disease
- This plasticity has upside and downsides
o Upside: you need myelin plasticity to learn
complex skills, important for cognition (ability to
think/ working/ concentration)
o Downside: the proliferative capacity can also
cause the OPCs grow into brain tumors: gliomas
3
,Glioma
Ø Heterogenous brain tumor, arise from OPCs, but they can adapt all kinds of glial
characteristics, sometimes they look like astrocytes, sometimes like microglia
Ø Often accompanied by cognitive impairment
Ø Treated by surgical removal of the tumor, chemo and radiation therapy
OPScs in gioma
o Cell of origion
o Esssential for cognitive functioning which is impaired in glioma
o Neuron-glioma synapses are similar to neuron-OPC synapses
Evidence for demyelination in glioma
- There is some evidence for demyelination in glioma
- It seems that not only the myelin around the tumor, but
everywhere in the brain seems to be impaired > but this has
never been proven
Ø Increased MBP levels in CSF of glioma patients (Nakagawa et
al., 1994)
o Cerebral spinal fluid of glioma patients contains high
levels of myelin protein (MBP)
o MBP is usually locked into the myelin sheets, if you
have this protein in your CSF, it means that there was
some myelin breakdown and the proteins are being
recycled
Ø Gliomas almost always reoccur, the tumor is di]use, tumor
and healthy tissue are tangled up in each other, so when brain surgery is done, they
cannot remove all tumor out
Ø Glioma cells migrate throughout the brain via white matter tracts (Huang-
Hobbs et al., 2023) using myelin
Ø Perhaps signs of demyelination (Wang et al., 2019).
Ø This is teachers research, we don’t have to know all of this
White matter and cognition in glioma
- White matter abnormalities in glioma
o Lower white matter fiber density and lower integrity of white matter
tracts throughout the brain in glioma patients
o This correlates with cognitive impairment
- Cognitive impairment in glioma is likely caused by white matter
abnormalities
Current research
- Multiscale imaging to elucidate the role of white matter myelin and
oligodendroglial abnormalities in cognitive impairment in glioma
4
,In vitro patient-derived OPC characterization
- Tissue that surrounds the tumor is being investigated
- They make the oligodendrocytes to survive in culture
- They study what these oligodendrocytes can do, are
they already impaired themselves or not?
o They are put into proliferation and
di]erentiation > the cells do great, they can
proliferate and di]erentiate and form myelin
sheets (green is myelin protein)
Tissue characterization of oligodendroglia in glioma
Ø DAPI staining for all nuclei
Ø OLIG2 staining for oligodendrocytes
Ø ASPA staining for mature myelinated oligodendrocytes
o There are still many mature oligodendrocytes
>> The oligodendrocytes are functioning super well in glioma healthy
surrounding brain matter
Multiscale investigation
Ø Integrate data to elucidate how cellular abnormalities lead to the white matter
disturbances that correlate with cognitive impairment in glioma
Essential to understand the intricate relationship between glioma and white matter
- Glioma arise in the white matter
- Glioma preferentially occur in white matter tracts that mature later in life
- Glioma recur in the white matter
- Glioma carry white-matter cell characteristics
- Glioma cells migrate through white matter
- Glioma gives white-matter related symptoms; cognitive impairment and complex
symptomatology related to its exact location
Ø There are so many links between this disease and the white matter in the healthy part of
the brain
Anatomy of white matter structures in the brain
Major fiber systems in the telecephalon
Three di]erent types of white matter structure:
o Association fibers
- White matter bundles or fibers that connection
brain areas on the same hemisphere of the brain
(either from left to left or right to right)
o Arcuate fasciculus: arcuate fibers go in
an arch (in green)
o Inferior/ superior longitudinal fasciculus
o Occipitofrontal fasciculus
o Cingulum
5
, o Commisural fibers
- Fibers that cross from left to right hemisphere or
right to left
o Corpus callosum
o Projection fibers
- Fibers that project from the cortex all the way down
to the brainstem into the spinal cord
o Internal capsule
https://www.youtube.com/watch?v=PazaHElk6wc
>> The longitudinal fasciculus connects the frontal, parietal, occipital and
temporal cortex for the integration of sensory information
>> A subset of fibers in the superior longitudinal fasciculus forms the
arcuate fasciculus
- It connects language areas:
o Broca’s area (production of language)
o Wernicke’s area (comprehension of language)
Occurrence heatmap of insular
glioma
Ø Heatmap of where insular
gliomas occur
Ø Yellow parts is where the gliomas occur
Ø If we look into more detail in white matter structures, the
two white matter structures are a]ected in insular gliomas
o Uncinate fasciculus
o Inferior occipitofrontal fasciculus
Insular white matter tracts
- Most gliomas occur in following insular white matter tracts
o Uncinate fasciculus
o Inferior occipitofrontal fasciculus
Uncinate fasciculus
- Location
o Connects the frontal lobe (specifically, the anterior parts including
the orbitofrontal cortex) to the temporal lobe (especially the
anterior temporal cortex)
- Function
o Significant role in emotional regulation, social cognition, and
memory
6
, >> Indeed, cognitive symptoms are common in insular glioma!
Inferior occipitofrontal fasciculus
- Location
o Connects the frontal lobe to the occipital lobe, specifically the
inferior parts
- Function
o Involved in visual processing and the integration of visual information with other
cognitive functions
>> Indeed, visual symptoms are common in insular
glioma!
Insular white matter tracts
Ø This image shows that both the uncinate fasciculus and
inferior fronto-occipital fasciculus have a degraded
integrity/ the integrity of these white matter bundles
goes down/ is not preserved
Fiber bundles that diNer between insular glioma patients and
controls
Ø Then they looked into all the other white matter tracks that
go through the insular cortex
Ø All of these have a di]erent integrity, less functional than in
a healthy brain
o Left arcuate fasciculus
o Left inferior longitudinal fasciculus
Arcuate fasciculus
- Location
o Connects the frontal lobe to the parietal lobe and the temporal
lobe in the dominant hemisphere (usually the left hemisphere) of
the brain
- Function
o Plays a crucial role in language processing, particularly in language production,
comprehension, and repetition
Inferior longitudinal fasciculus
- Location
o Runs along the ventral (bottom) aspect of the brain, connecting
the occipital lobe to the temporal lobe
- Function
o Visual processing and recognition of complex visual stimuli,
including faces and objects
7
,Corpus callosum: involved in frontal glioma
- Location
o Connects the two cerebral hemispheres of the brain
- Function
o Facilitates communication and information exchange between
the left and right hemispheres
Cingulate fasciculus: involved in frontal glioma
- Location
o Encircles the cingulate cortex and runs along the inner surface of
the brain’s hemispheres
- Function
o Involved in various functions, including emotion regulation,
memory, and attention
Corona radiata and internal capsule: involved in parietal glioma
- Location
o Runs between the basal ganglia and the thalamus to the cerebral
cortex
- Function
o Communication between di]erent regions of the brain,
transmission of sensory and motor information, as well as higher-order cognitive
and sensory-motor integration signals
Major fiber systems in the telecephalon
Patient-derived oligodendrocytes form arcuate fibers, inferior occipitofrontal fasciculus
and corpus callosum radiation
Tissue from frontal gyri with arcuate fibers
8
, Synapse biology
Lecture 1 – Introduction and synapse probability
Introduction
Ø The CNCR brings together neurobiologists, clinicians, psychologists, geneticists and
physicists in research teams to generate joint research
9
