Scientists first proved in vivothat emit gamma-aminobutyric acid neurons in the early stages of development are exciting, and then become inhibitory. The GABA neurons of the hippocampus, a three-day mice had a trigger effect, but the seventh day became the brake. In the visual cortex such cells since birth had a vast effect. The authors of an article published in the journal Science Advances, note that because of this heterogeneity modulation of the activity of the GABA neurons (e.g., in the treatment of epilepsy) at an early age can lead to unpredictable results.
The GABAergic interneurons (cells that produce as a neurotransmitter gamma-aminobutyric acid) are the main braking system of the mammalian brain and is important for proper configuration of brain rhythms. They are necessary for the formation of neural networks in the developing brain, but their functions and the mechanism of the influence on embryonic and postnatal development of the nervous system are poorly understood.
There is a hypothesisaccording to which in the young brain’s GABAergic neurons do not inhibit, but rather stimulate the neural target cells and sinhroniziruete the activity of neurons. With the maturation of networks of cerebral cortex GABAergic cells have in this case to restructure their operations and become brake. Still to confirm this hypothesis in vivo failed — even the cells, which in culture are exciting, in the brain of live animals showed a braking activity.
Yasunobu Murata (Yasunobu Murata) and Matthew Colonnese (Matthew Colonnese) from the George Washington University has changed the activity of GABAergic hippocampal neurons in newborn mice. For that immediately after birth the mice injected virus that are delivered in GABAergic cells of the hippocampus the receptors of two types: one was initiated by the neurons, if it were clozapine-N-oxide and the other suppressed their activity when exposed to salvinorin B. the researchers Then injected mice with one of these substances and watched the activity of the hippocampus using a bundle of microelectrodes.
Excitation of GABAergic neurons clozapine-N-oxide on the third day from birth led to increased activity of pyramidal cells in the hippocampus. Salvinorin B, on the contrary, twice reduced the number of nerve impulses and the amplitude of the rhythms in the hippocampus. On the seventh day after the birth, the dependence is reversed: when you activate GABAergic neurons pyramidal cells of the hippocampus inhibited. In this age of GABAergic neurons did not affect the amplitude of the rhythms in the hippocampus. So, in the early postnatal period, cells that produce GABA, are stimulating and modulate the rhythms of the hippocampus, and then the rhythms become independent and GABA-neurons — brake.
Then the action of GABAergic cells tested in the visual cortex. In this area, on the third and on the seventh day after the birth of the GABA neurons had inhibitory activity and did not affect rhythmic activity in the hippocampus.
Due to heterogeneity (depending on age and areas of the brain) influence of GABA-neurons at an early age attempt to modulate their activity at the system level (for example, in the treatment of epilepsy) can lead to unpredictable results. To test the effect of excitation or inhibition of GABAergic neurons in the whole brain, the virus with receptors introduced in the entorhinal and somatosensory cortex (these areas send projections to the hippocampus).
Excitation of GABA neurons in the entorhinal and somatosensory cortex led to the suppression of the activity of pyramidal hippocampal neurons, and inhibition of GABA-secreting cells to the opposite effect. Then, the brake signals of neurons outweigh excitatory activity of hippocampal interneurons.
Finally, the researchers tested the reliability of the results and the mechanism of action of GABAergic neurons by a different method. For this used the tools of optogenetics: using the virus in the nerve cells of the delivered light-activated proteins-channels for anions (usually, the opening of anion channels leads to inhibition of the cells). The virus introduced in the GABA neurons or hippocampal pyramidal cells in the same area and the visual cortex. In the second case, the light-sensitive proteins to mimic the receptors to GABA pyramidal neurons — perhaps they cause the different effect of GABA-neurons at different ages.
Optogenetics inhibition of GABAergic hippocampal neurons led to suppression of the activity of pyramidal cells at the age of three days, but to be activated on the seventh day after birth. In the visual cortex of the opening of the light-sensitive anionic channels weakened the activity of pyramidal cells in the hippocampus three days the effect was the opposite — anionic conductivity, even briefly, lead to electrical excitation of cells. On the seventh day the dependence was opposite. Scientists have concluded that the heterogeneous influence of the GABAergic neurons is mediated anion receptors to GABA.
The lack of GABAergic cells occurs in some neurodegenerative diseases such as chorea Huntington. To compensate for dead cells, scientists learned how to turn brake gliu in neurons — but only in mice.