Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo.

Multiphoton imaging (MPI) is widely used for recording activity simultaneously from many neurons in superficial cortical layers in vivo. We combined regenerative amplification multiphoton microscopy (RAMM) with genetically encoded calcium indicators to extend MPI of neuronal population activity into layer 5 (L5) of adult mouse somatosensory cortex. We found that this approach could be used to record and quantify spontaneous and sensory-evoked activity in populations of L5 neuronal somata located as much as 800 μm below the pia.

Toxicity assessment of intravitreal triamcinolone and bevacizumab in a retinal explant mouse model using two-photon microscopy.

Purpose: Intravitreal drug administration leads to high intraocular concentrations with potentially toxic effects on ocular tissues. This study was an assessment of the toxicity of triamcinolone and bevacizumab in living retinal explants using two-photon (2P) microscopy.

Methods: Wild-type mice received intravitreal injections of triamcinolone, bevacizumab, or vehicle.

Linking synaptic plasticity and spike output at excitatory and inhibitory synapses onto cerebellar Purkinje cells.

Understanding the relationship between synaptic plasticity and neuronal output is essential if we are to understand how plasticity is encoded in neural circuits. In the cerebellar cortex, motor learning is thought to be implemented by long-term depression (LTD) of excitatory parallel fiber (PF) to Purkinje cell synapses triggered by climbing fiber (CF) input. However, theories of motor learning generally neglect the contribution of plasticity of inhibitory inputs to Purkinje cells.

Cerebellar LTD and pattern recognition by Purkinje cells.

Many theories of cerebellar function assume that long-term depression (LTD) of parallel fiber (PF) synapses enables Purkinje cells to learn to recognize PF activity patterns. We have studied the LTD-based recognition of PF patterns in a biophysically realistic Purkinje-cell model. With simple-spike firing as observed in vivo, the presentation of a pattern resulted in a burst of spikes followed by a pause.

Feed-forward inhibition shapes the spike output of cerebellar Purkinje cells.

Although the cerebellum is thought to play a key role in timing of movements on the time scale of milliseconds, it is unclear how such temporal fidelity is ensured at the cellular level. We have investigated the timing of feed-forward inhibition onto interneurons and Purkinje cells activated by parallel fibre stimulation in slices of cerebellar cortex from P18-25 rats. Feed-forward inhibition was activated within approximately 1 ms after the onset of excitation in both cell types.

Neuronal microcircuits: frequency-dependent flow of inhibition.

New work suggests that feedback inhibition of neurons in the hippocampus is mediated by two distinct microcircuits. Interneurons targeting a neuron's soma are triggered by onset of activity, while those targeting distal dendrites are recruited by sustained activity. These circuits may thus convey information about the timing and rate of activity, respectively.