On the neuronal basis of cognition : cell-type specific circuitry and functions of the prefrontal cortex

Sammanfattning: This thesis recapitulates the history of research, and current knowledge, of the prefrontal cortex (PFC) in order to provide a context for the included scientific articles. The evident, but ill-defined, symptoms of a perturbation of the PFC is still a conundrum to neuroscientists. Though considered a source of cognition, or intellect, the quest to define an overall framework of how cognition is processed, or built, in the PFC, is very much an ongoing endower. The work presented in this thesis address both the structural architecture, as well as the electrophysiological properties, underlying the unique functions of the PFC. Chapter 2 of this thesis discusses the unique connectivity of the PFC and its relevance to a functional understanding of the neuronal computations present in the PFC. In this context, PAPER I reports the local and whole-brain connectivity scheme of discrete neuronal types within the PFC by the use of a novel rabies virus tracing system. Through carefully mapping monosynaptic inputs to four separate neuronal types, we describe that all connectivity traits defining the PFC, hold true for multiple neuronal types: the appearance of subnetworks within the PFC, the distinct thalamic innervation, and the high interconnectivity between PFC subregions. The third Chapter describes various electrophysiological properties present in the PFC, and more specifically, the occurrence of gamma oscillations, and their specific relevance to cognition. PAPER II and III report on the relevance of parvalbumin expressing interneurons for the generation of gamma oscillations in the rodent cortex. PAPER III further describes the presence of gamma oscillations during correct allocation of attention, and the frequency dependent activity of parvalbumin expressing interneurons. The temporal organisation of parvalbumin expressing interneurons, and the functional activity of excitatory neurons are, at this stage, only observations. However, the activity of parvalbumin expressing neurons was shown to be vital for the attentive state, and consequently, crucial for the network activity of the PFC. In summary, the work of this thesis, portrays cell type specific activity, as well as local and long-range circuitry of the rodent PFC. Although the concept of cognition may differ in appearance in mice as compared to humans, there is a common acceptance that key elements in the structure and function of the brain have been conserved through evolution, allowing for translatability. Ultimately, by carefully disentangling and observing small pieces of the circuitry and neuronal computation at a time, we can begin to build a framework for the neuronal underpinnings of cognition.