Last week we studied the auditory system and sound localization. This week we will move to the development of the brain. We will explore the genesis of neurons and how they form connections. We will also study synaptic plasticity, elimination of synapses and programmed cell death. Finally, we will consider alterations in synaptic capacity.
Creation of Neurons
The generation of neurons has three phases: proliferation, migration and differentiation. The neurons of the brain generate from the walls of the ventricles. They copy their DNAs and divide to two radial glial cells or more familiarly, stem cells. These radial glial cells continue dividing rapidly until they form all the neurons and glial cells of the cortex. This phase is called proliferation and most of the generated cells are never replaced.
Next, neurons migrate to their destinations. The radial glial cells emit fibers that help their daughter cells in navigation. On the contrary, one third of the cells wander horizontally to the cortex. Reelin-protein regulates the assembly of the cortex. The neural precursory cells migrate in phases to form the cortex from inside out:
- Subplate cells
- Layer VI cells of the cortical plate
- Layer V cells of the cortical plate
The last phase in the generation of neurons, differentiation, is a process that starts before cell migration and finishes after it. It begins with the neuron sprouting neurites which develop into an axon and dendrites. The differentiation is determined by the programming of the neuron and through intercellular signals. Pyramidal cells are characterized by a large dendrite and an axon that faces the opposite direction. The marginal zone of the brain secretes protein semaphorin 3A that repels pyramidal cell axons and attracts dendrites. This causes the dendrites to move towards the brain surface. The neurite differentiation is often regulated by diffusible molecules even in other areas.
Elimination of Cells and Synapses
From before birth till adolescence the connections of the brain are refined. However, as we grow it becomes important for our brain to establish a balance between newly formed neurons and synapses and the elimination of them. It is surprising to know that a large-scale reduction of all newly formed neurons and synapses is a source of significant refinements in the brain. It is perhaps one of the most remarkable features of nerves to maintain an accurate number of synaptic connections.
Programmed Cell Death
An entire population of neurons is eliminated during pathway formation. The term programmed signifies that it happens as a result of genetic instructions provided to these cells. After axons reach their targets and synapse formation has begun, there is a gradual decline in the number of presynaptic axons and neurons. Cell death reflects competition for trophic factors, life-sustaining substances and resources that are available in limited quantities. This process is believed to produce the proper match in the number of pre and postsynaptic neurons.
Alterations in Synaptic Capacity
Each neuron has a definite number of synapses which could be attached to its dendrites and soma. This is known as synaptic capacity of the neuron and it varies throughout the nervous system. This capacity peaks during our years of development and then slowly declines as we mature.
It is believed that during the initial stages a muscle fiber receives input from several different motor neurons. But eventually this polyneuronal innervation is lost and each muscle fiber receives synaptic input from a single alpha motor neuron. Retention of polyneuronal innervation occurs when activities of muscle fibers are silenced but stimulation of the muscles accelerates the elimination of all but one input. Some observations have revealed that the initial loss of postsynaptic AchRs occurs during synapse elimination. This is followed by the disassembly of the presynaptic terminal and retraction of the axon branch. The insufficient receptor activation in active muscles is said to be the cause of receptors to disappear. Even if all the AChRs are blocked, the synapses remain because the muscle is also silent.
Cortical Synaptic Plasticity
In theory, there are two “rules” which define synaptic modification in the cortex, according to the classical Hebbian synaptic plasticity:
- The synapse formed by the presynaptic axon is strengthened, when the presynaptic axon is active, and the postsynaptic neuron is strongly activated under the influence of other inputs.
- The synapse formed by the presynaptic axon is weakened, when the presynaptic axon is active, and the postsynaptic neuron is weakly activated by other inputs, i.e., it is out of sync with the other neurons.
The key in strengthening and weakening of a synapse is correlation; a single synapse alone cannot influence the firing rate of the post-synaptic neuron, to do this the synapse must be strongly correlated with other inputs arriving on the same post-synaptic neuron. Hebbian plasticity focuses on the simultaneous activity of the pre- and the post synaptic neuron. Long-term potentiation (LTP) is strengthening of the synaptic transmission by strong activation of NMDA receptor and more calcium ion influx, whereas weak activation of the receptors and especially the lower influx of calcium ions trigger the opposite of LTP, long-term depression (LTD).
There is a fair amount of ongoing research about cortical plasticity in general, for example papers like “Heterosynaptic Plasticity in Cortical Interneurons”  and “Synaptic Plasticity in A Visual Cortical Region Induced by Early-Deafness” . The former is a research paper published in the Journal of Neuroscience and its aim was to review research about different kinds plasticity which doesn’t follow the classical Hebbian plasticity. All in all, the review indicates that the plasticity of the cortical regions is much more complex in reality in comparison to the classical theory.
The latter is a Master Thesis paper from Virginia Commonwealth University, and it focuses on presenting a research how early-deafness influences the plasticity in the visual cortex of the neurons of early-deaf cats. The results indicated that there is a notable influence on dendritic spine density and dendritic spine diameter. These two numerical quantities are well-known indicators of synaptic plasticity in the cortex, so the research indicated that loss of hearing has effects on the synaptic plasticity of the neurons in the visual cortex. The research was done with the neurons of cats, but a varying form of such plasticity can most likely be seen in the neurons of humans as well.
- Caya-Bissonnette, L. Heterosynaptic Plasticity in Cortical Interneurons.
Journal of Neuroscience 26 February 2020, 40 (9) 1793-1794;
- Kay, John M. Synaptic Plasticity in A Visual Cortical Region Induced by Early–Deafness. Master Thesis, Virginia Commonwealth University. 2020.