Control of resting ion currents by adrenergic receptors in the prefrontal cortical pyramidal neurons (mPFC) in rats of different ages
In neuropsychiatric diseases, the activity of neurons in the prefrontal cortex is impaired by small neurotransmitters: dopamine, serotonin, acetylcholine or noradrenaline. These neurotransmitters activate metabotropic membrane receptors, which cause changes in resting membrane currents and, consequently, changes in the activity of neurons. Disruption of the functioning of these systems leads to pathologically altered activity of neurons in the prefrontal cortex and disturbs the organism's behavior in the environment. In order to correct the disturbed control of the activity of prefrontal cortex neurons by small neurotransmitters, it is necessary to understand the mechanism of their action at the cellular level in healthy individuals. The control of prefrontal cortex neurons by adrenergic receptors is relatively little known. It is believed that the signal transmission in the prefrontal cortex neurons from adrenergic receptors to cell electors (ion channels) is disturbed in, inter alia, post-traumatic stress disorder, schizophrenia, mood disorders and anxiety disorders. The occurrence of these pathologies depends on the age of the individual. The aim of the project is to investigate the mechanisms responsible for the control of resting membrane currents in the pyramidal neurons of the prefrontal cortex by adrenergic receptors. In particular, I intend to investigate: • What subtypes of membrane adrenergic receptors are responsible for altering resting membrane currents in pyramidal neurons? • What subtypes of ion channels (cellular effectors) responsible for resting membrane currents are controlled by adrenergic receptors? • Which secondary membrane and / or cytoplasmic messengers mediate signaling from adrenergic receptors to ion channels? • Is the control of resting membrane currents by adrenergic receptors different in juvenile, adolescent and adult rats? The aim of the project is to investigate the mechanisms responsible for the control of resting membrane currents in the pyramidal neurons of the prefrontal cortex by adrenergic receptors. Membrane currents will be recorded in slices from layer V pyramidal neurons of the prefrontal cortex. Sections will be taken from the medial prefrontal cortex of young (20 days old), adolescent (40 days old) and adults (60 days old) rats. Recordings of currents will be made by the method of perforated patches at the temperature of 34 ° C with the use of gramicidin dissolved in the liquid in a pipette. If necessary, membrane currents will be recorded from dispersed neurons using the classical method of stabilizing the potential on the entire surface of cell membranes (whole-cell vollagc-clamp). Adrenergic agonists, cell effectors blockers and the intracellular signal transduction system others will be added to the recording chamber or to the fluid in the pipette. The influence of these compounds on resting membrane currents will be analyzed. In my research I will define the process of signal transmission from adrenergic receptors to cellular effectors in the pyramidal neurons of the prefrontal cortex. These studies are important because: a. Impaired function at one of the signal transduction stages may lead to the development of neuropsychiatric diseases, and b. All elements of the signal transduction pathway are a potential target for action for biologically active substances administered to restore normal neuronal function.