Cell-type specific astrocyte activation is driven by cortical top-down modulation

Abstract

Cortical projections to cortical and subcortical targets provide top-down modulation that shapes neuronal performance, including gain control and excitation-inhibition balance. However, the contribution of astrocytes to this process remains poorly understood. In the olfactory bulb, the first relay station of odor information processing, bottom-up input is transmitted from olfactory sensory neurons to mitral/tufted (M/T) cells, which project to the olfactory cortex. Context- and state-dependent top-down modulation arises from feedback projections originating in the anterior piriform cortex (aPC) that target granule cells (GCs). We examined how astrocytes respond to bottom-up and top-down neuronal activity using confocal Ca{superscript 2} imaging, cell-type-specific optogenetics, electrical stimulation, and single-cell electrophysiology. We found that Ca{superscript 2} signals in astrocytes are selectively triggered by action potential-dependent ATP release from GCs while M/T cells failed to elicit significant astrocytic responses. Although synaptic input from M/T cells depolarized GCs, it was insufficient to induce action potential firing and subsequent astrocyte activation. By contrast, glutamatergic top-down input from the aPC evoked sustained GC firing, leading to ATP-dependent Ca{superscript 2} signaling in astrocytes. Our results reveal an unappreciated level of complexity in neuron-astrocyte communication, highlighting its cell-type specificity as well as its context- and state-dependence.