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

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

Prefrontal Parvalbumin Neurons in Control of Attention

SummaryWhile signatures of attention have been extensively studied in sensory systems, the neural sources and computations responsible for top-down control of attention are largely unknown. Using chronic recordings in mice, we found that fast-spiking parvalbumin (FS-PV) interneurons in medial prefrontal cortex (mPFC) uniformly show increased and sustained firing during goal-driven attentional processing, correlating to the level of attention. Elevated activity of FS-PV neurons on the timescale of seconds predicted successful execution of behavior. Successful allocation of attention was characterized by strong synchronization of FS-PV neurons, increased gamma oscillations, and phase locking of pyramidal firing. Phase-locked pyramidal neurons showed gamma-phase-dependent rate modulation during successful attentional processing. Optogenetic silencing of FS-PV neurons deteriorated attentional processing, while optogenetic synchronization of FS-PV neurons at gamma frequencies had pro-cognitive effects and improved goal-directed behavior. FS-PV neurons thus act as a functional unit coordinating the activity in the local mPFC circuit during goal-driven attentional processing

Cell-type-specific representation of spatial context in the rat prefrontal cortex

Summary: The ability to represent one’s own position in relation to cues, goals, or threats is crucial to successful goal-directed behavior. Using optotagging in knock-in rats expressing Cre recombinase in parvalbumin (PV) neurons (PV-Cre rats), we demonstrate cell-type-specific encoding of spatial and movement variables in the medial prefrontal cortex (mPFC) during goal-directed reward seeking. Single neurons encoded the conjunction of the animal’s spatial position and the run direction, referred to as the spatial context. The spatial context was most prominently represented by the inhibitory PV interneurons. Movement toward the reward was signified by increased local field potential (LFP) oscillations in the gamma band but this LFP signature was not related to the spatial information in the neuronal firing. The results highlight how spatial information is incorporated into cognitive operations in the mPFC. The presented PV-Cre line opens the door for expanded research approaches in rats