Neuromodulator-mediated control of spatial and nonspatial information processing in the hippocampus

Abstract

How the brain implements learning is a long-standing question in neuroscience research. Many studies have indicated a critical role of the hippocampus in establishing memories of facts and episodes. As episodic memories require the association of many different sensory events in the environment, the hippocampus integrates multimodal information acquired from sensory systems. The brain area that sends major afferent inputs to the hippocampus, the entorhinal cortex, can be further divided into two subareas, the medial and lateral entorhinal cortex, each of which primarily transfers either spatial or nonspatial information to the hippocampus. The proper control of these two information streams is essential for constructing neuronal representations of the environment in hippocampus. To understand this process, my studies have focused primarily on the projection from the entorhinal cortex to area CA1, the temporoammonic pathway. Although this pathway has been relatively unexplored, recent studies have suggested that it plays a unique role in hippocampal function. I investigated how the temporoammonic synapses influence hippocampal function from three different perspectives; in single-neuron studies, local-circuit analyses, and behavioral manipulations. I propose that the temporoammonic pathway gives rise to a unique functional circuit in the hippocampus, which allows for the independent control of spatial and nonspatial information processing. Neuromodulators are a key component to this control as they differentially influence two streams of information from the entorhinal cortex. Finally, I describe my studies on the pathophysiology of schizophrenia-like behaviors at a neuronal circuit level. A mouse model of schizophrenia, generated by maternal immune activation, displays several behavioral abnormalities relevant to schizophrenia patients. We found that hippocampal slices prepared from these mice exhibit altered synaptic properties in the temporoammonic pathway. The mice also exhibit behavioral abnormality in novel object recognition. Taken together, my studies shed light on two information streams in hippocampal circuits. Anatomical or neuromodulatory-based disturbance of this control may underlie some of the behavioral abnormalities observed in several mental disorders.