The long-term goal of this research program is to provide an understanding of the synaptic organization of intracortical circuits that interconnect visual cortical areas at different levels of the cortical hierarchy. Vision depends on the activation of multiple cortical areas. The substrates for this coordination are feedforward (FF) and feedback (FB) connections that link lower with higher cortical areas. Single unit recordings suggest that pre-attentive vision depends on FF circuits, whereas FB circuits play a role in attentive vision. These distinct functions depend on the circuit-specific enhancement and suppression of firing. Our observations suggest that this might be achieved by controlling inhibition, which differentially regulates recurrent excitation in FF and FB circuits. The findings further show that each pathway has different frequency-dependencies of synaptic excitation and inhibition, which makes suppression and enhancement stimulus-specific. Differences in inhibition in FF and FB circuits emerge post-natally and involve strengthening of inhibition in the FF pathway while inhibition in the FB pathway remains frozen at a weaker level, present at eye opening. It is not known whether these pathway-specific changes involve a redistribution of different types of inhibitory neurons, the modification of the strength and dynamic properties of excitatory inputs to inhibitory neurons and/or alterations of the inhibitory outputs of these neurons. To distinguish these possibilities, we propose to use transgenic mice, which express Green Fluorescent Protein (GFP) either in parvalbumin (PV)- or calretinin/somatostatin-immunoreactive (i.e. non-PV) GABAergic neurons to study the physiology and anatomy of their synaptic inputs and outputs in FF and FB circuits.
The first aim will use whole cell recording and dye filling of GFP interneurons to determine whether FF and FB pathways are connected to different subtypes of PV and non-PV neurons. Experiments proposed in Aim 2 will characterize the excitatory inputs to PV and non- PV neurons. Experiments in Aim 3 will use paired recordings from synaptically connected GFP interneurons and pyramidal neurons together with light and electron microscopy to determine the strength and dynamic properties of inhibitory outputs to pyramidal neurons. These studies will provide insight into customizing inhibition for balancing excitation in FF circuits for bottom-up processing at high spatio-temporal resolution and FB circuits for top-down processing of object saliency and attentional selection.
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