TY - JOUR T1 - Respiratory Modulation of Spontaneous Subthreshold Synaptic Activity in Olfactory Bulb Granule Cells Recorded in Awake, Head-Fixed Mice JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8758 LP - 8767 DO - 10.1523/JNEUROSCI.0311-15.2015 VL - 35 IS - 23 AU - Isaac A. Youngstrom AU - Ben W. Strowbridge Y1 - 2015/06/10 UR - http://www.jneurosci.org/content/35/23/8758.abstract N2 - Although the firing patterns of principal neurons in the olfactory bulb are known to be modulated strongly by respiration even under basal conditions, less is known about whether inhibitory local circuit activity in the olfactory bulb (OB) is modulated phasically. The diverse phase preferences of principal neurons in the OB and olfactory cortex that innervate granule cells (GCs) may interfere and prevent robust respiratory coupling, as suggested by recent findings. Using whole-cell recording, we examined the spontaneous, subthreshold membrane potential of GCs in the OBs of awake head-fixed mice. We found that, during periods of basal respiration, the synaptic input to GCs was strongly phase modulated, leading to a phase preference in the average, cycle-normalized membrane potential. Subthreshold phase tuning was heterogeneous in both mitral and tufted cells (MTCs) and GCs but relatively constant within each GC during periods of increased respiratory frequency. The timing of individual EPSPs in GC recordings also was phase modulated with the phase preference imparted by large-amplitude EPSPs, with fast kinetics often matching the phase tuning of the average membrane potential. These results suggest that activity in a subset of excitatory afferents to GCs, presumably including cortical feedback projections and other sources of large-amplitude unitary EPSPs, function to provide a timing signal linked to respiration. The phase preference we find in the membrane potential may provide a mechanism to dynamically modulate recurrent and lateral dendrodendritic inhibition of MTCs and to selective engage a subpopulation of interneurons based on the alignment of their phase tuning relative to sensory-driven MTC discharges. ER -