Mechanisms of Axon Guidance

The axons are slender processes of uniform diameter arising from the hillock. There is usually only one unbranched axon per neuron.

* The axon ends in a cluster of terminal buttons, which are small knobs that secrete chemicals called neurotransmitters.

The end of the axon spread into some shorter fibers that have swellings on the ends called synaptic knobs. The synaptic knob has a number of little saclike structures in it called synaptic vesicles. Inside the synaptic vesicles are chemicals hung in fluid, which are molecules of substances called neurotransmitters which are inside a neuron and are going to transmit a message. Neurotransmitter are released into the synapse from synaptic vesicles. The neurotransmitter molecules bind to receptor sites on the releasing neuron and the second neuron or glands or even muscles causing a reaction.

A study was performed by Merzenich in 1986 in which the index finger of a monkey was amputated, and signals were monitored in the corresponding part of the monkey's corticol map (3). Since the monkey's finger was no longer attached to the body, the logical hypothesis is that there would be no signals coming from the finger's area to the nervous system. However, every time the two fingers adjacent to that of the amputated one were touched, there were nerve impulses in the spinal cord. This led the scientists to believe that there are existing axon branches that become unbranched after normal input ends.

Doctor Linqun Luo is a professor here at Stanford and currently teaches neurobiology and does research as the principal investigator in the Luo Lab as a member of the Howard Hughes Medical Institute. His primary research area is the human brain focusing on neural circuits and how they function, how precise are the connections, how they develop. To this end his lab is using fly and mouse models to study their various circuits, centering mainly on the olfactory, and exploring the early development of neural networks in mammals (Luo Lab Bio). In order to write this commentary on the topic “How do neurons connect with each other”, I have chosen two pieces to read. The first, from Science magazine, outlines the main issues, goals, and paths the world is taking to understand to understand neuroscience including the research being done to answer the question in his topic. The second paper, from Cell Press, is a much more technical paper which outlines one of the pathways Luo isolated in the olfactory cortex of mice and how their neurons may connect.

Fig. __ Feed-forward projections from the eyes to the brain and topographic mapping. In each eye the visual field on the left and right of the fovea (the cut goes right through the fovea!) projects to different cortical hemispheres: the ipsilateral retina projects to the ipsilateral visual cortex, and the contralateral retina crosses the contralateral cortex (hemifield crossing in the optic chiasma). The first synapse of the retinal ganglion cells is in the lateral geniculate nucleus (LGN), but information from the left (L) and right (R) eye remains strictly separated. The LGN consists of six layers, layers 1 and 2 are primarily occupied by the magnocellular pathway, and 3–6 by the parvocellular. Information from both eyes comes first together

These layers are made of myelin, produced by Schwann cells that are assigned early in the organism’s development. As these layers develop they become tightly packed around the axons, and the main benefit of this coating is that it prevents the exiting and entering of ions for a distance along the axons. This protection allows the ions to travel further and cause action potentials at a faster rate (Norton and Cammer, 1984). Action potentials are caused by the influx of sodium ions followed by the slow efflux of potassium ions. The process of rapid action potentials jumping from one node to the next is called salutatory conductance (Black et al., 1991).

How are medially-positioned progenitors affected by diffusible signals? The number of neurons belonging to populations found near or at the centre of the dorsoventral axis of the cord is influenced by signal levels, including Shh and BMPs. A moderate concentration of BMP signaling is needed to generate the correct number of medial interneurons. In zebrafish mutants in which a particular BMP protein is functionally reduced, there was a resulting increase in Lim1+ interneurons (medial interneurons) post-mitotically (Nguyen et al., 2000). Interestingly, further BMP reduction decreases medial interneuron counts, illustrating the fine balance of BMP levels that is needed to establish appropriate medial interneuron expression. Perturbing natural

Brett reached into a clogged snow blower to clear the chute while it was still running. He completely severed one finger and partially severed another on his left hand. After lengthy surgery to reattach his fingers, he has regained much of his motor ability but has lost some of his sensory function. What factors are involved that affect the regeneration of Brett’s neurons and neuron function?

Lightly myelinated Aδ fibers and unmyelinated C fibers have thinner axons and a higher threshold of activation. Nociceptors of Aδ fibers can be either mechanosensitive or thermosensitive. Polymodal nociceptors (of C fibers), may respond to both mechanical and thermal stimuli, as well as chemicals [261-263]. When nociceptors are activated, the fibers transmit action potentials along the axon to the spinal cord [264, 265]. The spinal cord mediates sensory and motor communication between the periphery and the brain, and is organized into four regions; cervical, thoracic, lumbar, and sacral. The gray matter contains cell bodies of neurons and glia and is divided into the dorsal horn, intermediate column, lateral horn, and ventral horn. The dorsal horn is comprised of sensory nuclei that receive and process incoming sensory information [266], and like the rest of the spinal gray matter, is organized histologically into parallel laminae based on the size and density of neurons [267]. In general, laminae I to IV are involved in exteroceptive sensation whereas laminae V and VI are involved in proprioceptive sensations [263]. Nociceptors terminate in the dorsal horn laminae in a

Studies on nerve fibers’ longitudinal growth, axons’ regeneration and structural plasticity of axons and dendrites illustrated that they are restricted to short distances and limited spatial dimensions in the CNS. Scientists recognized that neural repair required plasticity, sprouting, and regeneration, which was limited within the adult CNS. However, once adult CNS axons from multiple areas successfully regenerated into peripheral nerve grafts in the spinal cord, brain, or optic nerve, scientists discovered the key role of local tissue microenvironment in determining the extent of growth. Scientists discovered neurite growth inhibitor factors enriched in myelin such as Nogo-A, myelin proteins, MAG and OMgp, semaphorins and ephrins, and chondroitin sulphate

a. Injured axons activate macrophages which in turn clear myelin and axon debris efficiently away from damaged nerve. Simultaneously, macrophages produce growth factors that facilitate Schwann cell migration and axon regeneration (Rotshenker, S. 2011).

Synaptic transmissions, otherwise referred to as neurotransmissions, are important to look at when investigating how physiological changes have an effect psychologically as changes have an affect on behaviour. Neurons are nerve cells that send electrochemical messages to the brain in the response from a stimuli and neurotransmitters transfer information from the neurons by diffusing across synapses. Synaptic transmission is the process by which neurons transfer the information; the neurotransmitters are released by neurons and bind to the receptors of postsynaptic neurons.

As soon as the electrical signal reaches the end of the axon, mechanism of chemical alteration initiates. First, calcium ion spurt into the axon terminal, leading to the release of neurotransmitters “molecules released neurons which carries information to the adjacent cell”. Next, inside the axon terminal, neurotransmitter molecules are stored inside a membrane sac called vesicle. Finally, the neurotransmitter molecule is then discharged in synapse space to be delivered to post synaptic neuron.

In the research paper “The Role of Calcium in the Rapid Adaption of an Insect Mechanoreceptor”, researchers aimed to identify whether calcium entry into the cell is correlated with neuronal adaption. To address this question researcher varied the concentration of calcium in the extracellular space of the cell in addition to applying calcium blocking agents (cobalt and cadmium), and by applying a calcium ionophore (antibiotic A23187). Three primary findings pertaining to these substances were derived from the experiment. The most important finding was that increasing the extracellular concentration of calcium did not increase the rate of adaption and instead reduced the rate of adaption. Secondly, researchers found that the presence of cobalt reduced the rate of adaption, the opposite of what they had originally expected. Lastly, no significant difference in adaption rate was found for solutions containing the antibiotic A23187.