According to one dogma of neuroscience, neurotransmitter population was thought to be fixed and immutable throughout life once developmental stages have passed. For over 100 years, a central assumption in the field of neuroscience has been that the brain of the adult mammals should remain structurally constant. New neurons, as well as new neurotransmitters were thought not to be added to the adult mammalian brain and that the production of new neurons would occur only during development and would stop before puberty.However, a new study by Dulcis et al.
has shown that sensory stimuli can lead to a switch in neurotransmitter expression in adult rat brain. These changes in neurotransmitter have eventually explained the causes of many seasonal affective disorders, as well as the depression and anxious behaviors that one might experience during the wintertime. In his experiment, Dulcis and his colleagues had exposed adult rats to different photoperiods and observed for any changes that occur within these animals’ brain.As a result, rats that have their photoperiods switched from long day (19 hours light – 5 hours dark) to long night (5 hours light – 19 hours dark) had reacted to the situation by changing the neurotransmitters in certain neurons of their hypothalamus (an area of the brain that produces hormones that control body temperature, hunger, moods, sleep, etc.
from dopamine to somatostatin. According to Dulcis’ report, short-day exposure has increased the number of dopaminergic neurons and the release of dopamine (a neurotransmitter that has many functions in the brain, and one of them is to signal positive or reward experiences) in rat’s hypothalamic nuclei, whereas long-day exposure has an opposite effect.Interestingly, at the same time, the number of somatostatin (a neurotransmitter that inhibits the pituitary gland’s secretion of growth hormone and thyroid stimulating hormone) in these rats’ hypothalamic nuclei had showed an inverse relationship with the dopamine population, suggesting that changes in photoperiods are driving causes that lead to a neurotransmitter switch between dopamine and somatostatin.Moreover, changes in numbers of tyrosine hydroxylase (an enzyme in the dopamine synthetic pathway) and somatostatin are also paralleled to changes in the mRNA expression, meaning that changes in expressions of neurotransmitters indeed occur with new mRNA transcripts, not from changes in translation of pre-existing ones. Based on Dulcis’ experiment, sensory activation, in the form of changes in the light-dark cycle, has shown to have the ability to induce such neurotransmitter switching, and therefore, the idea of neurotransmitter population being fixed has become invalid.Not only the switching of neurotransmitters, Dulcis also finds that presynaptic changes in transmitter identity also correspond to changes in respective postsynaptic receptor populations.
For example, when rats were exposed to long-day photoperiods, their number of dopaminergic neurons would decrease, which leads to a corresponding down-regulation of the respective dopamine receptors (D2Rs) on the postsynaptic neurons.However, although somatostatin receptor expression would remain constant unlike postsynaptic dopamine receptors, which change to match with the presynaptic dopamine, somatostatin interneurons of the hypothalamus can make synapses on corticotropin-releasing factor (CRF) neurons, thus changes in somatostatin cell numbers would significantly influence the levels of CRF in the cerebrospinal fluid (CSF).In agreement with these findings, the number of CRF in the cerebrospinal fluid of adult rats was abundant when the number of somatostatin neuron expanded resulted from the exposure to the long-day photoperiod, and decreased as the dopamine receptor expression rose after exposure to the short-day photoperiod.In response to the changes of light-dark cycle, not only presynaptic neurons/neurotransmitters would be switched, but the corresponding postsynaptic neurons are also affected, as well as the amount of corticotropin-releasing factor neurons being released into the cerebrospinal fluid of the brain. Since neurotransmitters, such as dopamine can have a subsequent effect on the brain in which it signals positive and rewarding experiences, the switching of neurotransmitters indeed also have behavioral consequences.As Dulcis tested rats on the elevated plus maze and in a forced swimming test, the result has shown that those rats that are exposed to short day photoperiod, where there is an increased number of dopamine neurons, tend to be more active in which they spend more time exploring the open arm of the elevated plus maze and also spend a longer time swimming whereas those that exposed to a long-day photoperiod had resulted in an opposite situation, which makes perfect sense for these nocturnal animals.
As for human, because humans are prone to be more active during the day, an example of the effect resulted from the changing in neurotransmitters population is the depressive or anxious behavior in the wintertime where there are fewer days than night. During the winter, dopamine transmitter population in human hypothalamus is to be transformed or switched to somatostatin, thus many people often have a tough time waking up in the morning and also feel very tired throughout the day.However, since not all neurons switch transmitters in response to changes in daylight, Dulcis and his team hoped to find out more about the molecular differences between those neurons that do and those that do not. If transmitter switching does lead to behavior consequences or other diseases, by understand the generalization of the molecular mechanism of neurotransmitter switching and be able to identify the transmitter system that is deregulated in a disease, it will be possible to find new treatment strategies.
In regard to the effects of neurotransmitter switching on human behaviour, by understand and be able to use sensory stimuli to provide a therapeutic approach, one could reverse the negative balance of faulty neurotransmitter system and restore the normal function in the mature nervous system of those that have neurological or psychiatric disorders, such as Parkinson’s diseases patients. Unlike what has been stated about the fixation of neurotransmitter population, Dulcis and his colleagues have been able to show the changes in the number of neurotransmitters within the hypothalamus through various experiments with adult rats.Not only transmitter switching, Dulcis and his team also discovered that presynaptic changes in transmitter identity are also supposed to match up with changes in postsynaptic receptor populations. As a result to this, transmitter switching has somewhat contributed to depressive behaviors, as well as neurological disorder. By understand and explore more about macroscopic mechanism of the changes of neurotransmitters, there might a breakthrough in neurology in which methods of treating patients with neurological disorders would be more effective and new treatment strategies might also be invented.
