Unbiased methods to assess the firing activity of individual neurons in the neocortex have revealed that a large proportion of cells fire at extremely low rates (<0.1 Hz), both in their spontaneous and evoked activity. Thus, firing in neocortical networks appears to be dominated by a small population of highly active neurons. Here we use a fosGFP transgenic mouse to examine the properties of cells with a recent history of elevated activity. FosGFP-expressing layer 2/3 pyramidal cells fired at higher rates compared to fosGFP− neurons, both in vivo and in vitro. Elevated activity could be attributed to increased excitatory and decreased inhibitory drive to fosGFP+ neurons. Paired-cell recordings indicated that fosGFP+ neurons had a greater likelihood of being connected to each other. These findings indicate that highly active, interconnected neuronal ensembles are present in the neocortex and suggest these cells may play a role in the encoding of sensory information.

A defining feature of cortical layer 2/3 excitatory neurons is their sparse activity, often firing in singlets of action potentials. Local inhibitory neurons are thought to play a major role in regulating sparseness, but which cell types are recruited by single excitatory synaptic inputs is unknown. Using multiple, targeted, in vivo whole-cell recordings, we show that single uEPSPs have little effect on the firing rates of excitatory neurons and somatostatin-expressing GABA-ergic inhibitory neurons but evoke precisely timed action potentials in parvalbumin-expressing inhibitory neurons. Despite a uEPSP decay time of 7.8 ms, the evoked action potentials were almost completely restricted to the uEPSP rising phase (~0.5 ms). Evoked parvalbumin-expressing neuron action potentials go on to inhibit the local excitatory network, thus providing a pathway for single spike evoked disynaptic inhibition which may enforce sparse and precisely timed cortical signaling.

A longstanding goal in biomedical imaging, the control of light inside turbid media requires knowledge of how the phase and amplitude of an illuminating wavefront are transformed as the electric field propagates inside a scattering sample onto a target plane. So far, it has proved challenging to non-invasively characterise the scattered optical wavefront inside a disordered medium. Here, we present a non-invasive scattering compensation method, termed F-SHARP, which allows us to measure the scattered electric-field point spread function (E-field PSF) in three dimensions. Knowledge of the phase and amplitude of the E-field PSF makes it possible to optically cancel sample turbulence. We demonstrate the imaging capabilities of this technique on a variety of samples, and notably though vertebrate brains and across thinned skull in vivo.