Alterations of specific cortical GABAergic circuits underlie abnormal network activity in a mouse model of Down syndrome.

Down syndrome (DS) results in various degrees of cognitive deficits. In DS mouse models, recovery of behavioral and neurophysiological deficits using GABAR antagonists led to hypothesize an excessive activity of inhibitory circuits in this condition. Nonetheless, whether over-inhibition is present in DS and whether this is due to specific alterations of distinct GABAergic circuits is unknown.

Modulation of Coordinated Activity across Cortical Layers by Plasticity of Inhibitory Synapses.

In the neocortex, synaptic inhibition shapes all forms of spontaneous and sensory evoked activity. Importantly, inhibitory transmission is highly plastic, but the functional role of inhibitory synaptic plasticity is unknown. In the mouse barrel cortex, activation of layer (L) 2/3 pyramidal neurons (PNs) elicits strong feedforward inhibition (FFI) onto L5 PNs.

Unaltered Network Activity and Interneuronal Firing During Spontaneous Cortical Dynamics In Vivo in a Mouse Model of Severe Myoclonic Epilepsy of Infancy.

Severe myoclonic epilepsy of infancy (SMEI) is associated with loss of function of the SCN1A gene encoding the NaV1.1 sodium channel isoform. Previous studies in Scn1a(-/+) mice during the pre-epileptic period reported selective reduction in interneuron excitability and proposed this as the main pathological mechanism underlying SMEI.

Two-photon calcium imaging in the intact brain.

The calcium ion is a fundamental second messenger that plays crucial roles in the pathophysiology of brain cells. In this chapter, we will focus on the measurement of calcium fluctuations as a reporter of cellular excitability of both neurons and glial cells in the intact central nervous system. We will first describe the methodological aspects of in vivo two-photon fluorescence calcium imaging and then review recent data highlighting the ways in which this technique is revolutionizing our understanding of brain circuits at the cellular level.

Three-dimensional in vivo scanning microscopy with inertia-free focus control.

The acquisition of high-resolution images in three dimensions is of utmost importance for the morphological and functional investigation of biological tissues. Here, we present a laser scanning two-photon microscope with remote and motionless control of the focus position. The movement of the excitation spot along the propagation direction is achieved by shaping the laser wavefront with a spatial light modulator.