Inhibitory Postsynaptic Potential - Interesting Studies

Interesting Studies

Inhibitory postsynaptic potentials can be inhibited themselves through a signaling process called “depolarized-induced suppression of inhibition (DSI)” in CA1 pyramidal cells and cerebral Purkinje cells. In a laboratory setting step depolarizations the soma have been used to create DSIs, but it can also be achieved through synaptically induced depolarization of the dendrites. DSIs can be blocked by ionotropic receptor calcium ion channel antagonists on the somata and proximal apical dendrites of CA1 pyramidal cells. Dendritic inhibitory postsynaptic potentials can be severely reduced by DSIs through direct depolarization.

Along these lines, inhibitory postsynaptic potentials are useful in the signaling of the olfactory bulb to the olfactory cortex. EPSPs are amplified by persistent sodium ion conductance in external tufted cells. Low-voltage activated calcium ion conductance enhances even larger EPSPs. The hyperpolarization activated nonselective cation conductance decreases EPSP summation and duration and they also change inhibitory inputs into postsynaptic excitation. IPSPs come into the picture when the tufted cells membranes are depolarized and IPSPs then cause inhibition. At resting threshold IPSPs induce action potentials. GABA is responsible for much of the work of the IPSPs in the external tufted cells.

Another interesting study of inhibitory postsynaptic potentials looks at neuronal theta rhythm oscillations that can be used to represent electrophysiological phenomena and various behaviors. Theta rhythms are found in the hippocampus and GABAergic synaptic inhibition helps to modulate them. They are dependent on IPSPs and started in either CA3 by muscarinic acetylcholine receptors and within C1 by the activation of group I metabotropic glutamate receptors. When interneurons are activated by metabotropic acetylcholine receptors in the CA1 region of rat hippocampal slices, a theta pattern of IPSPs in pyramidal cells occur independent of the input. This research also studies DSIs, showing that DSIs interrupt metabotropic acetylcholine-initiated rhythm through the release of endocannabinoids. An endocannabinoid-dependent mechanism can disrupt theta IPSPs through action potentials delivered as a burst pattern or brief train. In addition, the activation of metabotropic glutamate receptors removes any theta IPSP activity through a G-protein, calcium ion – independent pathway.

Inhibitory postsynaptic potentials have also been studied in the Purkinje cell through dendritic amplification. The study focused in on the propagation of IPSPs along dendrites and its dependency of ionotropic receptors by measuring the amplitude and time-course of the inhibitory postsynaptic potential. The results showed that both compound and unitary inhibitory postsynaptic potentials are amplified by dendritic calcium ion channels. The width of a somatic IPSP is independent of the distance between the soma and the synapse whereas the rise time increases with this distance. These IPSPs also regulate theta rhythms in pyramidal cells. On the other hand, inhibitory postsynaptic potentials are depolarizing and sometimes excitatory in immature mammalian spinal neurons because of high concentrations of intracellular chloride through ionotropic GABA or glycine chloride ion channels. These depolarizations activate voltage-dependent calcium channels. They later become hyperpolarizing as the mammal matures. In rats specifically this maturation occurs during the perinatal period when brain stem projects reach the lumbar enlargement. Descending modulatory inputs are necessary for the developmental shift from depolarizing to hyperpolarizing inhibitory postsynaptic potentials. This was studied through complete spinal cord transections at birth of rats and recording IPSPs from lumbar motoneurons at the end of the first week after birth.

Glutamate, an excitatory neurotransmitter, is usually associated with excitatory postsynaptic potentials in synaptic transmission, however, a study completed at the Vollum Institute at the Oregon Health Sciences University demonstrates that glutamate can also be used to induce inhibitory postsynaptic potentials in neurons. This study explains that metabotropic glutamate receptors feature activated G proteins in dopamine neurons that induce phosphoinositide hydrolysis. The resultant products bind to inositol triphosphate (IP3) receptors through calcium ion channels. The calcium comes from stores and activate potassium conductance, which causes a pure inhibition in the dopamine cells. The changing levels of synaptically released glutamate creates an excitation through the activation of ionotropic receptors, followed by the inhibition of metabotropic glutamate receptors.