GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

Figure 2

A model for GABA_AR-mediated synchronization mechanisms. The left panel shows a group of pyramidal cells that are common postsynaptic targets of an inhibitory GABA neuron. Perisomatic-targeting GABA neurons such as that in the scheme produce stronger inhibition than GABA neuron subtypes that target the dendrites. The right panel shows, above (black trace), the membrane potential of the GABA neuron which remains at rest before and after firing a sequence of four action potentials. The red traces below show the membrane potential simultaneously recorded from the postsynaptic pyramidal neurons, which are firing in response to a continuous excitatory input. Note that, before the GABA neuron starts firing, the pyramidal cells fire in an asynchronous manner. Shortly after the first GABA neuron spike, an inhibitory postsynaptic potential (IPSP) is produced (first black arrow) which simultaneously inhibits the firing of all pyramidal neurons. After the IPSP-mediated inhibition decays, the pyramidal neurons fire in nearly synchrony. Note that a similar postinhibition synchronization is observed with each of the IPSPs evoked by the interneuron spikes (each IPSP is denoted by a black arrow). Once the GABA neuron stops firing, pyramidal cell activity rapidly becomes asynchronous. Also note that a single action potential in a GABA neuron would synchronize the pyramidal cells only once, whereas production of a synchronized oscillation requires rhythmic GABA neuron firing. An oscillation episode composed of four cycles is shown in the figure. The production of synchronized oscillations via this mechanism may be impaired by various alterations of GABA_AR-mediated synaptic inhibition in schizophrenia (see Figure 1 and main text).