Cholinergic control in the midbrain spatial attention network [electronic resource]

Neural activity that is periodic in the gamma band (25-90 Hz) occurs in many regions of the brain. The strength of this periodic activity is modulated dynamically during specific cognitive states, including during spatial attention. Local synchronization of neural activity in the gamma band has been proposed to be essential for selectively routing and enhancing the transmission of sensory information to downstream networks and for synchronizing activity across networks. Modulations of gamma power are thought to play a key role in mediating the enhanced neural and behavioral sensitivity associated with attention. Although such modulations of gamma power have been observed widely in a range of cognitive states, the precise mechanisms that regulate gamma power, and that underlie the influence of gamma-periodic activity on sensory information processing remain unclear. This dissertation studies the avian midbrain spatial attention network to investigate the neural mechanisms by which gamma oscillations are regulated and spread across networks. The avian midbrain network includes the multilayered optic tectum (OT; superior colliculus in mammals) and interconnected inhibitory and cholinergic nuclei located in the midbrain tegmentum. Each region contains a topographic map of space. This network combines information about the relative strengths of competing sensory stimuli together with descending information from the forebrain to compute a categorical representation of the highest priority location for attention and gaze. The prioritized location is represented in the OT space map by focal, persistent, high power gamma oscillations in the local field potential (LFP), and by spike-field coherence in the ascending neural activity from that location in the OT space map to the forebrain. This midbrain network interacts with the forebrain (frontoparietal) attention network to select the next location for spatial attention. Previous research demonstrated that the midbrain network contains its own gamma generator and provided preliminary evidence that the power of midbrain-generated gamma oscillations is regulated by cholinergic modulation. In the first study (Chapter 2), I reveal that cholinergic activation of neurons expressing non-[alpha] nicotinic acetylcholine receptors directly drives inhibition in the gamma generator and switches the network into a primed state capable of producing high amplitude oscillations. The special properties of this mechanism alter gamma power rapidly and persistently. I propose that similar mechanisms operate in other networks, but particularly in networks that require rapid, dynamic modulation of gamma power, such as those controlling selective attention. In a second study (Chapter 3), I investigate the mechanisms by which midbrain gamma oscillations influence an ascending, thalamus-projecting circuit within the midbrain network. Thalamic and forebrain responses to sensory stimuli synchronize to gamma rhythmic activity in the midbrain network. Inactivation of the cholinergic Ipc eliminates gamma power in ascending midbrain circuits, and prevents the gamma-rhythmic synchronization of thalamic activity. Thus, the Ipc controls the spread of the gamma-periodic selection signal within the midbrain network, and is critical for transmitting that signal to forebrain regions. What mechanisms underlie this control? I describe multiple mechanisms that may contribute to the influence of cholinergic signaling provided by gamma-rhythmic activation of the Ipc, on a visual-thalamus projecting circuit located within the OT. The results suggest that activation of complimentary mechanisms acts to sustain strong gamma-periodic activity in ascending midbrain circuits, gating gamma-rhythmic synchronization across midbrain and forebrain regions. In a third study (Chapter 4), I describe my efforts to adapt optogenetic techniques for use in chickens. In Chapters 2 and 3 I report a wide variety of mechanisms by which acetylcholine release influences neurons in multiple OT layers. A major source of acetylcholine in the midbrain network, the Ipc, releases acetylcholine with gamma periodicity, across all OT layers. In order to test the influence of physiologically relevant spatial and temporal patterns of Ipc activation on the midbrain spatial attention network, I developed optogenetic tools for use in chickens. I report that viral vectors developed for use in mammals are ineffective in chickens. In addition I demonstrate that high genomic titer avian-strain adeno-associated viruses (A3V) rapidly and robustly infect chicken neurons, and can be used to induce expression of both fluorophores and opsin-fluorophore fusion proteins.

Advisor: Huguenard John primary advisor. Thesis advisor
Knudsen Eric I. primary advisor. Thesis advisor
Hestrin Shaul
Moore Tirin
Ricci Anthony advisor. Thesis advisor