Lecture notes

Neuroscience 3 Lecture notes

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Module
Neuroscience (BIME09012)

Institution
The University Of Edinburgh (ED)

The course will explore how we sense, feel, motivate, behave, learn and remember. The processes and neural basis of sensation, cognition, motivation and behaviour, and the ways they may be studied (deconstructed) at systems, cellular and molecular levels will be illustrated by coverage of specific ...

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Uploaded on May 29, 2024
Number of pages 100
Written in 2023/2024
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Neuroscience Lecture Notes
L1. Into to NS3
A general theme in neuroscience is analysis and integration across different levels of
investigation and explanation.
The goal of this field is to understand the biology underlying functional outputs of the brain,
including questions like:
1. How do structures and actions of the brain and nervous system produce
behaviour and experience?
• how do predators identify, locate, and catch their prey?
• how does a migratory bird return to its nest site?
• what brain mechanisms underlie emotions?
• how do we know where we are?
2. How do behaviour and experience modify the brain? The brain and nervous system
are plastic. Experience can affect number or size of neurons, or the number or strength
of connections between neurons in development and in adulthood
• e.g. visual experience can influence development of the auditory system in
young barn owls
• e.g. in a sea slug, learning a task involves strengthening connections between
particular neurons in its nervous system
• e.g. extensive experience as a taxi-driver results in expansion of a region of the
brain (the posterior hippocampus) involved in spatial navigation.
see Bear, Connors & Paradiso Neuroscience Exploring the Brain, 3rd/4th eds

Functional approaches to studying neuroscience
We need to be able to describe and measure the functional and/or behavioural output:
* like detailed acts or processes (structural description), e.g. analytical description of leg
movements might record successive positions of the limb, or contraction of different
muscles; sequence of arm entries that a rat displays when running through a maze
* results or functions (functional description) like state whether limb is being used in
walking, running, hopping, swimming
* accuracy of navigation on the maze, types of errors being committed, cognitive
processes needed to solve the maze, function of navigation (to escape aversive
stimulus, or to locate food)

Measurements of the correlates of behaviour:
* Histology, staining and microscopy; tracing of connections in post mortem tissue
* Imaging the living brain (e.g. MRI scans, fluorescent reporters)
* Recording of neural, metabolic and synaptic activity (EEG, single unit recording,
autoradiography, gene activation, PET, fMRI)
* Measuring neurotransmitters and neuromodulators released by neurons (e.g. microdialysis,
transgenic reporters)

Manipulations
* Study of human clinical cases or groups of patients with brain damage
* Experimental brain lesions/pharmacological inactivation in animals

,* Electrical/optical stimulation of the brain (optogenetics)
* Genetic manipulations (e.g. targeted mutations)

How to choose the species?
Close relationships between species that behave differently enable testing of hypotheses
about neural basis of differences.

Why does Neuroscience study different species
There is continuity of behaviour and biological processes among species
* Nature is usually conservative, e.g. a nerve impulse is essentially same
in jellyfish, cockroach, and human
* similarities may occur because they first arose in common ancestor
* similar solutions to problems evolved independently, e.g. colour vision
in insects, fish, reptiles, birds & mammals
e.g. ,
• Differences in behaviour and biology have evolved in adaptation to different environments
1) bats - some species are almost blind, using hearing to navigate & find prey, others are
visually oriented. This is an example of closely related species evolving different
solutions to a given problem.
2) owl - acute auditory localization; zebrafish - repair central nervous system. Chicken –
brain development

Different animal “models” offer different advantages:
- lab rat - morphology and behaviour similar to other mammalian species. Easy to keep
in lab
- Mouse, Drosophila, C. elegans, zebrafish easy genetics (mutations, transgenesis)
- Mollusks and other invertebrates - simple nervous systems

Treatment/understanding disease Some species are subject to same diseases as humans and
are therefore valuable models for investigation.
We can generate animal “models” to study (aspects of) human diseases, e.g. Alzheimer’s
Disease - mutant human genes linked with AD can be expressed in mice to study how those
specific mutated genes contribute to pathological features of the disease (in the absence of
other factors).

In Neuroscience 3:
1) Behaviours that rely on specific sensory systems:
• Visual system
• Auditory system
• Somatosensory system
• Olfactory system
2) The changing brain – how experience modifies the brain:
• In development
• To mediate learning and memory (anatomical organisation, cellular
and molecular mechanisms, e.g. LTP)
3) Systems that control various behaviours:
• Emotion
• Spatial navigation
• Sexual behaviour
4) Evolution of proteins enabling cognitive capacity

, 5) Study of non-behaviour outputs of the nervous system

L2. Nervous System Development
Developmental neuroscience is a field that explores how the nervous
system is formed, from early embryonic stages through adulthood.
• The human brain is perhaps the most complex object in our universe
and studying how such a complex structure is assembled offers insights
into its functioning not easily achievable from analysis of the adult brain
• Neural progenitor cells follow predictable stages of proliferation,
differentiation, migration, and maturation, but the mechanisms
controlling the progression through each stage are incompletely
understood.
• Characterising and treating neurodevelopmental disorders
• Injury repair processes are like those that occur in development

There is no effective treatment available for the following
neurodevelopmental disorders:

Key steps during the development of the nervous system
➔ Which factors control the subdivision of the brain into distinct functional areas?
➔ Which factors control the size of the brain?
➔ How is migration of neurons controlled
➔ How do neurons contact their target cells?

Early stages of neural development

➢ Nervous system is derived from the
neuroectoderm. Neural plate folds to the
neural tube. Neural tube extends along the
whole -body axis as a hollow cylinder
➢ The developing nervous system is
organised along 2 principal axis:
➢ The neural tube is subdivided into 4 neuromeres along
the Anterior/posterior axis:
➢ The 4 main subdivisions of the embryonic CNS and
mature adult forms
- Telencephalon: cerebral cortex, basal ganglia,
hippocampal formation, amygdala, olfactory bulb
- Diencephalon: thalamus, hypothalamus,
epithalamus, retina
- Mesencephalon: midbrain
- Metencephalon: pons and cerebellum
- Myelencephalon: medulla
- Caudal part of neural tube: spinal cord

, Regional patterning of the nervous system
Regionalisation: Process that divides the neuroectoderm up into
areas that will lay the basis for regional specialization of a
structure in the mature nervous system.
Positional information: Provides cells with information on their
location within the neuroepithelium
French Flag Model- Lewis Wolpert
Next to sheet of cells there is a specialised group of cells
(organizer) which produces a secreted molecule to act as a
morphogen. Sets up a concentration gradient of a morphogen
which can be measured by cells which differentiate to different
types of cells depending on their threshold.

Spemann and Mangold experiment discovered concept of embryonic induction:
consisted of a series of grafting’s in which some cells were removed from the dorsal side of
an amphibian embryo and then transplanted to the other side of a second embryo. The
transplanted dorsal cells caused the embryo to develop a second set of complete body
structures – a secondary body axis including a nervous system.
➢ This demonstrated that signals from the organizer tissue
could induce neighbouring cells to differentiate into
new structures – these cells must therefore retain their
ability or competence to adopt to other fates

Organisation of the embryonic and adult spinal cord

➢ Neural tube has signalling centres at the roof plate –
dorsal, and ventral – floor plate
➢ Opposing BMP and SHH signals drive dorsal/ventral
patterning of the neural tube: bmp at dorsal roof plate,
shh at bottom.

➢ Shh controls the formation of ventral
interneurons and of motor neurons in a
concentration dependent manner. Seen
using chick embryos, at different
concentrations of SHH, neural plate
tissue differentiated into different types
of neurons.
➢ Shh controls the progenitor domain
specific expression of several
homeodomain transcription factors:

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