UC San Diego

The mammalian brain contains many regions in which feedforward excitatory afferents impinge on neurons that are interconnected by recurrent excitatory circuits. The functional in vivo properties of feedforward versus recurrent excitation are poorly understood due to the technical difficulty of distinguishing between these two sources of excitation in individual neurons. To address these issues I developed novel techniques for measuring the in vivo functional properties of the specific neuronal circuits that impinge onto individual neurons. Chapters 1 and 2 describe how feedforward and recurrent excitation onto individual neurons in the mouse primary visual cortex respond to visual stimuli. In the primary visual cortex, individual neurons are tuned to specific features of visual stimuli namely their orientation, direction of movement, and retinal location of bright and dark regions. I examined the extent to which these sensory tuning properties are present in the thalamic versus intracortical excitation onto single cortical neurons using in vivo intracellular recording techniques during optogenetic silencing of cortical excitatory neurons to isolate thalamic excitation. These results reveal that the main tuning properties observed in the primary visual cortex, namely receptive field structure, orientation selectivity, and direction selectivity, are already present in the thalamic excitation onto individual neurons. Estimation of the intracortical excitation from the total excitation recorded in the absence of cortical silencing revealed that thalamic and intracortical excitation share similar tuning properties demonstrating that tuned feedforward thalamic excitation is amplified by recurrent intracortical excitation. Chapter 3 describes a novel photolabeling method that allows neurons with known in vivo functional properties to be studied in in vitro brain slice preparations in order to reveal their cellular, synaptic, and circuit properties. This technique helps bridge the gap between systems and cellular neuroscience and opens up new possibilities for understanding how neuronal circuits underlie neuronal function in the intact brain. Together, these novel experimental approaches allow us to understand a fundamental aspect of neuronal circuit operation: the transfer and integration of information via synaptic connections. Such knowledge will aid in our understanding of the neuronal mechanisms underlying sensation, learning, and behavior