Subtle alterations in how cortical network dynamics are modulated by different behavioral states could disrupt normal brain function and underlie symptoms of neuropsychiatric disorders, including fragile X syndrome (FXS). Using two-photon calcium imaging and electrophysiology we recorded spontaneous neuronal ensemble activity in mouse somatosensory cortex. Unanesthetized Fmr1–/– mice exhibited abnormally high synchrony of neocortical network activity, especially during the first two postnatal weeks. Neuronal firing rates were 3-fold higher in Fmr1–/– mice during whole-cell recordings manifesting Up/Down states (slow wave sleep, quiet wakefulness), likely due to a higher firing probability during Up states. Combined EEG/calcium imaging experiments confirmed that neurons in mutant mice have abnormally high firing and synchrony during sleep. We conclude that cortical networks in FXS are hyperexcitable in a brain state-dependent manner during a critical period for experience-dependent plasticity. These state-dependent network defects could explain the intellectual, sleep and sensory integration dysfunctions associated with FXS.

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 (Ͼ20 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) butwithalterationsinthesizeandstabilityofspinesandboutonsobservedinthisbrainarea.Thechangeswedescribeherelikelyresultinweaker synapses that are less capable of short-term plasticity in aged individuals, and therefore to less efficient circuits.

We used a needs assessment to guide the development of a longitudinal, multidisciplinary POCUS curriculum. Residents who completed all components showed substantial long-term gains in knowledge in all major applications and high use of and confidence in cardiac and pulmonary applications.