Neurobiology For Dummies. Frank Amthor
alt="Remember"/> A neuron’s dendritic tree may have thousands of excitatory and inhibitory synaptic inputs, each of which may be modulated in a complex pattern over time. The way different inputs to the neuron interact also depends on their locations in the dendritic tree. Inputs that are near to each other may interact in a nonlinear way, exhibiting thresholds, saturation, multiplicative interactions, and other complex interactions.
In most neurons, all the inputs and their interactions result in a net flow of current into the cell body, or soma, and the initial segment of the axon. If the voltage produced by this current is below threshold, it doesn’t produce any spikes. Above this threshold, the rate of action potentials, or spikes, is generally proportional to the net excitatory (depolarizing) current. The spikes are sent down the axon where, at the axon terminals, neurotransmitter is released. Neurons may release neurotransmitter on neurons a few tens of micrometers away or a meter or more away.
Moving our limbs: Motor neurons
Besides going to other neurons, the information that neurons transmit can also go to our muscles. All vertebrate neuromuscular transmission in vertebrates uses the neurotransmitter acetylcholine. The evolution of the nervous system is closely tied to the ability to move — animals have neurons, but plants don’t. The nervous system allows us to move based on the environment (sensation) and on previous experience (learning). The nervous system also enables muscles in different parts of the body to work in a coordinated way to perform complex behaviors. For example, putting one foot in front of the other and walking — which most people do every day — is actually a highly complex behavior. Think of all the muscles that need to work together just so you can take a few steps!
When Things Go Wrong: Genetics and Neurological Illness
Genetics is absolutely amazing: A random shuffle of genes from two parents get thrown together, producing a working nervous system from the proteins encoded. This nervous system is produced with 80 to 100 billion cells and at least 100 trillion synapses. Of course, the process doesn’t always have perfect results, and sometimes things go wrong. This section discusses some of these cases.
Nervous system disorders include some fairly well-understood sensory problems such as blindness, deafness, and motor disorders like myasthenia gravis (see Chapter 16), whose causes (but not necessarily cures) we know at the cellular level. Problems that affect mental functions are more complex, such as learning disabilities, schizophrenia, depression, bipolar disorder, and obsessive-compulsive disorder.
Mutations and transcriptional errors
We know that many nervous system disorders are genetically based, even though we may not always know the genetic origin. So, how do genetic disorders happen?
Genetic mutations — which you probably know something about if you’ve ever read a comic book — are one cause of these disorders. Reproduction starts with germ cells (egg or sperm cells) being generated during meiosis. In this process, alternating partial segments from the parents’ double-stranded DNA produce the offspring’s unique DNA.
In the complex process of assembling a single chromosome of DNA from the two parental chromosomes, errors happen. These errors are one kind of mutation. Here are the three most common single chromosome mutations:
Deletion: In deletion, a piece of a chromosome or sequence of DNA is missing. A partial sequence from neither parent ends up in the single chromosome of the egg or sperm, making that DNA shorter and missing the gene altogether.
Duplication: In duplication, a partial sequence of DNA from one parent is inserted twice.
Inversion: When inversion happens, a partial DNA sequence from one parent is inserted upside down in the offspring. As we discuss earlier in this chapter, DNA is always transcribed from the same direction, so when a partial sequence is inserted upside-down, the protein coded is completely different when it’s transcribed.
Here are a few well-known examples of genetic disorders:
Down syndrome: The most well-known example of a disorder with a known genetic cause is Down syndrome, which is caused by an extra chromosome 21 (trisomy 21). Down syndrome occurs in about 1 in 1,000 births.
Fragile X syndrome: This disorder is the most common inherited cause of intellectual disability. It results from an X chromosome mutation. The features of Fragile X syndrome are mental retardation and a number of noted physical, emotional, and behavioral issues.
Rett syndrome: Another inherited developmental brain disorder, Rett syndrome is characterized by abnormal neuronal morphology and reduced levels of neurotransmitters norepinephrine and dopamine.
Schizophrenia: Rather than being due to a single mutation, schizophrenia has many genetic causes. It is a serious mental disorder that is characterized by severely impaired thinking, along with emotional and behavioral issues.
Autism: This neurological disorder also has multiple genetic causes. As such, individuals with different mutations have somewhat different disorders of varying severity. Autism is called a “spectrum” disorder because its multiple genetic causes create a range of phenotypic characteristics, depending on the person. Characteristics range from severe retardation to slight social ineptitude.
Asperger’s syndrome: Typically, Asperger’s is included in the autism spectrum as autism without significant language delay or dysfunction. Like autism, Asperger’s appears to arise from multiple mutation locations, and correspondingly very different types and severities of symptoms.
Modifying genes: Fixing or Frankenstein?
What can be done about genetically based neurological disorders? Can we fix broken genes?
Animal research
A huge research endeavor is going on, involving transgenic animals (animals whose genome has been changed by transferring genes from another species or breed, or by eliminating these genes altogether). The genetic compositions of these animals are different from so-called “wild type” animals. Many animal lines with these different genetic compositions originally arose from random mutations in offspring. They were then selectively bred as “models” for human diseases.
Gene therapy
Human genetic manipulation may require both silencing a gene that produces a harmful protein and/or adding a gene to produce a needed one. This involves introducing exogenous DNA into the person’s cells. This DNA may come from another organism or be synthesized in a lab.
The general term for genetic manipulation in humans for medical reasons is gene therapy. Gene therapy can be done in developed organisms rather than germ lines in several ways. One is to physically restrict the injection of the introduced DNA, such as in the eye to treat blindness, so that the gene can’t get into any other body cells. Another way is using a tissue or cell type-specific promoter with the DNA so that it’s only expressed in particular tissues.
Typically, the introduced DNA is packaged within a vector that