Yuste C2 Flashcards
Parts of the Nervous System
Maps and brain modules
Modules are internally organized into maps. Neurons with different functions are systematically located in particular places within the module (ex: precise map between visual field and location of neurons in the visual cortex responding to those positions). –> Topographic maps.
Benefit of modules being organized in maps
Carefully laying out connections and corresponding functional properties might help minimize the total amount of wiring that the NS needs.
Stages of neural development
Neurulation
The pinching off of the neural tube from the epithelium of the embryo. The neural tube then floats in the embryo, and the proliferation of neurons from its walls makes the tube grow and change shape.
Patterning
When the uniform neural tube becomes specialized into regions. Involved are key regions of the embryonic NS called “organizers” which are regions that secrete molecules that can trigger/induce a specific change in other cells, creating molecular gradients.
Organizers
Secrete molecules, creating molecular gradients. Cells in the embryonic NS receive different concentrations of these molecules according to their positions along the three molecular gradients: rostro-caudal, dorsal-ventral, and medio-lateral. These molecular gradients create different combinations of molecular signals that are turned into intracellular cascades that activate TFs, which regulate gene expression –> gives rise to different cell types according to location along the three molecular gradients.
Neurogenesis
A step in which billions new neurons are generated in the ventricular zone of the neural tube. Neuronal progenitor cells move up and down, and their oscillatory movements lead to cell division, generating new neuroblasts each cycle. As they are born, these neuroblasts get pushes away from the centre of the tube to the periphery, making the tube thicker.
Migration
By climbing up the radial glial fibers that extend across the developing neural tube, neuroblasts migrate to away from the ventricular zone to the periphery/top. Then, they generate an axon.
Axonal growth and pathfinding
Each developing neuron extends an axon and navigates in the embryonic NS searching for a target neuron to connect with. This only happens in the NS. This is done by the growth cone.
Growth cone
A specialized structure at the tip of a growing axon. Its purpose is navigation via reading chemical signals. It is very specific. It is attracted forwardly chemo-attractant and repelled backwards by chemo-repellants.
Chemoaffinity hypothesis
The growth cone is repelled or attracted by chemicals/molecular markers secreted by or on the surface of other neurons (the molecules neurons secrete/have in their surface depends on their position in the 3D molecular gradient axes). The combination of attractive and repulsive chemical cues directs the growth cone to its correct target.
Synaptogenesis
The formation of synaptic connections. Incredibly precise and self-assembled.
Occurs when growth cones find the membranes from the body or dendrites of their target neurons. The growth cone and the target neuron exchange molecular signals, likely also mechanical ones, reacting accordingly.
Signals include inducing molecules from the axon, which generate expression and clustering of NT receptors –> sophistical post-S structure exactly opposed to axon.
Growth cone turns into mature pre-S terminal.
Victor Hamburger
German developmental neurobiologist, studied the NMJ. Noticed that there were 50% fewer motorneurons in the spinal cord of chick embryos at the end of development compared to earlier stages. Proposed that this was caused by massive cell death of neurons whose function was to match the number of motorneurons to the number of muscles.
Neurotrophins
Also trophin factors. Molecules secreted by the post-synaptic cell to the pre-S axon, which supports the survival of the preS neuron.
Possibly one way they prevent cell death is to block the apoptosis pathway. => Developing neurons are prone to die by suicide unless they are rescued.
NGF
Nerve growth factor. Discovered and purified by Montalcini and Hoffman. Promotes the survival of preS neurons, so serves two match the # of preS neurons and # of postS targets. The more postS cells, the more NGF secreted, the more preS neurons survive.
Synaptic refinement
First found in NMJ. Process of elimination of synapses between neurons and muscle cells through competition among axons for muscles.
Estimates: at least 50% of synapses in developing CNS disappear after birth.
Partly controlled by neuronal activity: neurons that are active together maintain their synapses between them.
Tello
Disciple of Cajal. Noticed that muscle cells in early development were each innervated by many axons. But, later in development, each muscle cell was innervated by one axon.
Donald Hebb
Use it or lose it: applies to neural circuits storing memories as well as the rearrangement of connectivity in the developing nervous system.
Wiesel and Hubel
Carried out an experiment in 1963 studying kittens and the visual cortex. Sewed shut one eye of kittens and allowed them to develop, and saw that depriving vision from one eye altered neural circuits in the visual cortex forever.
Imbalance in the competition of both eyes for the same cortical territory: the kittens became blind in that eye. Did not see the same things in adults.
They defined a critical period of neural development during which neuronal activity instructs which synapses make it and which ones are lost.
Critical periods
Most brain functions have one. Regulatory mechanisms could include neurotrophins, which help neurons survive and protect synapses from being pruned away. Another mechanisms seems to be NMDA glutamate receptor, which turns on only when the neuron receives synaptic inputs and fires at the same time – allows a Ca2+ influx which turns on IC pathways and gene expression.
Activity-dependent pruning of neural circuits.
Implications/benefits of critical periods
Guarantees that the NS is precisely matched to the environment in which the animal lives.
Sharpening topographic maps, responding faster and more precisely to sensory stimuli, adjusting the NS to the rest of the body, etc.
Seven principles of developmental neuroscience
Temporal logic – every step gives rise to the next.
Molecular cascades – developmentally important molecule (IC or EC) binds another molecules (usually a protein) which triggers a conformational change that activates it, leading it to bind another molecule to activate it…
Stable developmental states – system that has many interacting components can achieve stable states due to the fact that the components talk to each other; development depends on the aggregate. Molecular and genetic networks self-regulate in this way.
Molecular gradients – defining Cartesian axes of the embryo; neurons located in particular places have GPS style coordinates. Express molecular markers on the surface/secrete them (ZIP codes).
Stages – synapse is built in stages according to close interaction between the incoming axon and the neuronal target.
Pre and postS interaction – incoming axons are orderly organized in space => topographic organization.
Pruning – developing brain builds a massive connectivity matrix and sends its to the field (the environment) and lets neural activity prune away what isn’t needed.
Overview: neural development
The NS is built with a conserved design across evolution, creating structural modules that have specific functional properties. Using molecular mechanisms, these modules, often filled with maps, are self-assembled in stages. The initial ones are intrinsic and genetically determined, whereas the later ones are regulated by neuronal activity and lead to a massive elimination of neurons and connections. NS is carved to match the environment in which we grow up.
