The roles of Inhibitory neurons in neuropsychiatric diseases

Our research is focused on investigating the relationship between the dysregulation of synaptic function and neuropsychiatric diseases such as schizophrenia and autism spectrum disorders (ASD) by exploring the regulatory mechanism of inhibitory neurons-mediated synaptic transmission. Synapses are a specialized junction of cell-cell contacts that allow for communication between neurons. Synaptic transmission is mediated by neurotransmitters that are released from a presynaptic terminal and act on corresponding receptors on the postsynaptic dendrite. In the mammalian central nervous system, the most excitatory neurons use glutamate as a neurotransmitter while inhibitory neurons use GABA. Neuronal signal processing is mediated by the integration of both excitatory and inhibitory synaptic responses. Therefore, precise regulatory mechanisms must exist to maintain the balance of excitatory and inhibitory synaptic transmission “E/I balance”. It is becoming increasingly clear that neuropsychiatric diseases may arise from the dysregulation of inhibitory neuronal function which leads to a change in the E/I balance. This would suggest that the restoration of inhibitory function can be a possible direction for therapeutic direction.

How can we restore inhibitory function? To answer this question, we must understand how inhibitory neurons are activated by excitatory inputs and how the disease-related molecules dysregulate synaptic function. Unfortunately, not much is known about these important topics. Most of our knowledge on excitatory transmission for example is based on studies between two synaptically connected excitatory neurons, but our understanding of excitatory synapses on inhibitory neurons is limited.

The first research aim for my laboratory is the characterization of excitatory synaptic transmission on inhibitory neurons. The second research aim is to investigate the roles of autism-related genes, such as neuroligin, neurexin, and Shank in excitatory and inhibitory synaptic transmission. We will use a multidisciplinary approach, building on our experiences in electrophysiology and molecular biology techniques to study the role of inhibitory neurons and disease-related molecules with respect to the E-I balance in the hippocampus and cortex.

Rotation Projects

The Futai laboratory seeks highly motivated graduate students who have interest in the roles of risk genes of neuropsychiatric diseases, such as autism and schizophrenia, on neuronal function.Rotation students will typically work side-by-side with Kenny Futai or Postdoctoral Fellows, and give one laboratory meeting presentation at the conclusion of their rotation project.

Rotation projects

1. The roles of the risk genes of neuropsychiatric diseases on neuronal structure and synaptic function
2. The roles of the scaffold molecules in synapse maturation, synaptic transmission and synaptic plasticity
3. Characterization of gultamate receptors which express in interneruon