Page 12 - AN-2-1

Advanced Neurology The AIS structure and function

their AIS will be elongated and proximally shifted closer a previous study has reported a molecular remodeling of
to the soma . Moreover, electrophysiology recordings the AIS, which was observed in the surviving peri-infarct
[61]
have shown that input-deprived neurons tend to be more region after focal cortical stroke . Moreover, de novo AIS
[67]
excitable, indicating that to regulate neuronal excitability formation has been observed within the peri-infarct cortex,
and homeostasis as well as maintain neuronal circuit suggesting that stroke-induced axonal sprouting may
output, neurons might need to adapt to presynaptic activity contribute to the formation of new functional axons .
[67]
by altering their AIS properties.
In in vivo experiments using chicken embryos, Hiroshi 6. Conclusions
Kuba et al. found that depriving chickens of auditory input The AIS is a remarkable neuronal structure comprising a
(destroying the cochlea) resulted in the elongation of the complex assembly of membrane proteins, scaffold proteins,
AIS of chicken brainstem auditory neurons (Chick NM). cytoskeletal adaptors, and voltage-gated ion channels. The
In the experiment, 7 days after auditory input deprivation, precise molecular distribution of the AIS ensures proper
the AIS length increased to 1.7 times the original length. neuronal excitability by regulating the generation of APs.
The distribution of Na channels and the excitability of The dynamic properties of the AIS allow the regulation
+
neurons increased, but the density and distribution of Na of neuronal excitability in response to neuronal activities
+
channels barely changed . In addition, different decibels both inside and outside the cell, thereby maintaining
[61]
of auditory stimulation may cause the AIS to shorten or homeostasis and the output of neural circuits. Dendritic
lengthen, suggesting that the AIS can change its length AIS may play an important role in the homeostatic
according to the activity level of presynaptic neurons. regulation of physiological functions in the nervous system
due to its insensitivity to external stimulus. The AIS also
In addition, Grubb and Burrone have demonstrated demarcates the boundary between the dendritic-somatic
a distal shift in AIS location, up to 17 μm away from the and axonal compartments while allowing axonal proteins
cell body, after 48 h of in vitro culture of rat hippocampal to pass through. Moreover, certain structural properties
neurons under high-concentration K treatment (15 mM of the AIS, such as length and/or location, can change
+
potassium chloride [KCl]) to the extracellular fluid. In through activity-dependent manners. The structural
the AIS, AnkG and other associated proteins, such as Na plasticity of the AIS is known as an important factor for
+
channels and βIV-spectrin, moved accordingly, but there the establishment and maintenance of nervous system
was no observable change in AIS length. After washing, functions. During AIS plasticity, the proteins in the AIS
the AIS returned to its original position in relation to the may undergo a demolition and reconstruction process.
cell body, and after 48 h of treatment with 15 mM KCl, However, we still have very limited knowledge of the AIS.
neuronal excitability reduced, and a stronger current
stimulation was needed for the neurons to fire an AP . From research on the brain of Alzheimer’s disease
[60]
(AD) patients, we are aware that axonal pathology is
Our previous study has shown that after treating associated with neuroaxonal dystrophy and amyloid
cultured hippocampal neurons with 20 mM glucose for 3 h, plaque formation . Our previous study has also shown
[68]
the neurons from both rats and mice showed changes in AIS that AIS pathology may occur even before axonal
length or location but in different ways : in rat neurons, pathology . As a result of the key role AIS plays in
[40]
[54]
the AIS length became shorter, and the distance from the AP bursts, the dysfunction of AIS may lead to certain
cell body increased because the proximal end of the AIS was neurological diseases. For example, mutations in ion
pushed away from the cell body, while the distal end did not channel subtypes could cause epilepsy . In addition,
[48]
change; in mouse neurons, the AIS was longer, but there was ANK3 (gene encoding AnkG) mutation has been found
no change in distance from the cell body as the distal end of to be associated with some neuronal diseases, such as
the AIS moved away from the cell body, while the proximal bipolar disorder , intellectual disability , schizophrenia,
[69]
[70]
end of the AIS showed almost no change. However, in both and autism spectrum disorder [71,72] . In mouse models,
mouse and rat neurons, the dendritic AIS barely changed the loss of βIV-spectrin function resulted in ataxia and
after the 20 mM glucose treatment, indicating that even in central auditory deafness [73,74] . Moreover, patient with the
the presence of the same external stimulus, AIS plasticity pathogenic variant of SPNB4 (gene encoding human βIV-
varies between different types of neurons. spectrin) has also been associated with myopathies and
AIS plasticity can also occur under certain auditory neuropathies . Our previous study has shown
[75]
pathophysiological conditions. A previous study has that AnkG deficiency in the AIS could play a significant
shown AIS plasticity in barrel cortex L5 pyramidal neurons role in AD pathology . Therefore, restoring or preserving
[54]
in a mild traumatic brain injury model, where the AIS was the structure and function of the AIS will be an important
shortened and AP intensity was attenuated . Similarly, strategy for the treatment of these diseases.
[66]

Volume 2 Issue 1 (2023) 4 https://doi.org/10.36922/an.v2i1.274