Synaptic integration of corticocortical and higher-order thalamocortical inputs across the visual cortex: Direct connections between cortical regions (corticocortical pathways) and indirect connections between these regions via the higher-order thalamus are distinct streams of information that allow distant cortical regions to communicate in both feedforward and feedback directions. Yet, we know very little about how these separate pathways are integrated. This knowledge is necessary to understand how these pathways work together for normal cortical processing. By combining whole-cell patch clamp recordings with optogenetic stimulation of corticocortical and higher-order thalamocortical axon terminals in ex vivo cortical slice preparations, we will understand the synaptic mechanisms that link these pathways. We use the mouse visual system for this question because, compared to other sensory systems in the mouse, we have a rich background knowledge about the hierarchical organization of the various cortical regions downstream of the primary sensory cortical area (V1).
Functional diversity within the higher-order thalamus: The higher-order thalamus (such as the pulvinar in the visual system) has historically been an enigma, partially because of the highly variable sensory and motor deficits observed in both human and non-human animal subjects upon lesions in this structure: from effective blindness to spatial neglect. Such variability might be explained by considering the specific circuits in which higher-order thalamocortical neurons are embedded. We hypothesize that thalamocortical neurons within the higher-order thalamus exhibit distinct physiological properties and presynaptic corticothalamic and subcortical inputs based upon which cortical regions they connect, and in which direction (feedforward vs. feedback). We will test this idea using anterograde and retrograde transsynaptic tracing techniques combined with fluorescence-guided recording of pathway-specific higher-order thalamocortical neurons.
Dynamics of corticocortical and higher-order thalamocortical pathways during perceptual decision making: Mapping sensory inputs to appropriate motor commands depends on the proper flow of information across the cortex. To address how corticocortical and higher-order thalamocortical pathways interact to support these processes, we will use dual-color in vivo imaging techniques to simultaneously monitor the axonal activity of these pathways while mice make perceptual decisions. We are interested in testing whether optimal perceptual performance requires co-activation of corticocortical and higher-order thalamocortical pathways and how independent manipulation of these pathways affects specific aspects of performance, such as decision bias and discriminability.
Neuromodulation of higher-order thalamocortical/corticothalamic systems: Synaptic neurotransmitter release and postsynaptic responses (both determinants of synaptic strength) strongly depend on levels of chemical neuromodulators within the brain (e.g. acetylcholine and serotonin). Since specific thalamocortical and corticothalamic pathways involving the higher-order thalamus have previously been difficult to manipulate experimentally, we know very little about how neuromodulators influence synaptic signaling within these pathways. One of our major goals is to combine both ex vivo and in vivo approaches to understand how state-dependent changes in neuromodulatory activity influence the functional interactions between the higher-order thalamus and the cortex.
Integration of the higher-order thalamus in the cortico-basal ganglia loop: Interactions between the frontal cortex (motor, premotor, and prefrontal) and the basal ganglia are critical for motor planning and execution, and are impaired in neurodegenerative disorders such as Parkinson’s and Huntington’s disease. The motor thalamus is often considered a simple relay of basal ganglia activity that is sent back to the cortex. Yet, the higher-order portion of the motor thalamus (the ventromedial nucleus, VM) also receives strong corticothalamic input. Interestingly, while the corticothalamic inputs are excitatory, the basal ganglia inputs are inhibitory. We lack an understanding of how these excitatory-inhibitory interactions determine the dynamics of higher-order motor thalamocortical activity and how this activity ultimately influences frontal cortical circuits during motor planning and execution. A longer-term goal of the lab is to integrate many of the techniques we have used in the visual system to understand the role of the higher-order thalamus in the integration of cortical and basal ganglia inputs during motor behavior.
