Broadly tuned and respiration-independent inhibition in the olfactory bulb of awake mice.

Olfactory representations are shaped by brain state and respiration. The interaction and circuit substrates of these influences are unclear. Granule cells (GCs) in the main olfactory bulb (MOB) are presumed to sculpt activity reaching the cortex via inhibition of mitral/tufted cells (MTs). GCs potentially make ensemble activity more sparse by facilitating lateral inhibition among MTs and/or enforce temporally precise activity locked to breathing. Yet the selectivity and temporal structure of wakeful GC activity are unknown. We recorded GCs in the MOB of anesthetized and awake mice and identified state-dependent features of odor coding and temporal patterning. Under anesthesia, GCs were sparsely active and strongly and synchronously coupled to respiration. Upon waking, GCs desynchronized, broadened their tuning and largely fired independently from respiration. Thus, during wakefulness, GCs exhibited stronger odor responses with less temporal structure. We propose that during wakefulness GCs may shape MT odor responses through broadened lateral interactions rather than respiratory synchronization.

Altered synaptic dynamics during normal brain aging.

What is the neuroanatomical basis for the decline in brain function that occurs during normal aging? Previous postmortem studies have blamed it on a reduction in spine density, though results remain controversial and spine dynamics were not assessed. We used chronic in vivo two-photon imaging of dendritic spines and axonal boutons in somatosensory cortex for up to 1 year in thy1 GFP mice to test the hypothesis that aging is associated with alterations in synaptic dynamics. We find that the density of spines and en passant boutons (EPBs) in pyramidal cells increases throughout adult life but is stable between mature (8-15 months) and old (>20 months) mice. However, new spines and EPBs are two to three times more likely to be stabilized over 30 d in old mice, although the long-term retention (over months) of stable spines is lower in old animals. In old mice, spines are smaller on average but are still able to make synaptic connections regardless of their size, as assessed by serial section electron microscopy reconstructions of previously imaged dendrites. Thus, our data suggest that age-related deficits in sensory perception are not associated with synapse loss in somatosensory cortex (as might be expected) but with alterations in the size and stability of spines and boutons observed in this brain area. The changes we describe here likely result in weaker synapses that are less capable of short-term plasticity in aged individuals, and therefore to less efficient circuits.