Hippocampal microcircuit dynamics probed using optical imaging approaches

Abstract

Mammalian cortical structures are endowed with the capacity for plasticity, which emerges from a combination of the dynamics of circuit connectivity and function, and the intrinsic function of the neurons within the circuit. However, this capacity is accompanied by a significant risk: the capability to generate seizure discharges is also a property of all mammalian cortices. How do cortical circuits reconcile the requirement to maintain plasticity, but at the same time control seizure initiation? These issues come into particular focus in the hippocampus. The hippocampus is one of the main plasticity engines in the brain, and is also a structure frequently implicated in the generation of epileptic seizures, with temporal lobe epilepsy constituting the most prevalent form of epilepsy in the adult population. One aspect of hippocampal circuitry that is particularly prominent is its intimate interconnections with the entorhinal cortex. These interconnections create a number of excitatory synaptic loops within the limbic system, which, in addition to being important in cognitive function, can support reentrant activation and seizure generation. In the present review, using optical imaging approaches to elucidate circuit processing at high temporal and spatial resolution, we examine how two targets of entorhinal cortical input within the hippocampus, the dentate gyrus and area CA1, regulate these synaptic pathways in ways that can maintain functions important in generation of normal activity patterns, but that dampen the ability of these inputs to generate seizure discharges.

Dissecting the phenotypes of Dravet syndrome by gene deletion

“…As a complement to our studies of cortical interneurons, we tested the functional consequence of selective deletion of Na v 1.1 in CA1 horizontal stratum oriens lacunosum-moleculare (O-LM) cells. O-LM cells are critical for regulation of action potential firing of CA1 pyramidal cells and thereby exert important inhibitory control of circuit function and prevent epilepsy (Maccaferri and McBain, 1995;Pouille and Scanziani, 2004;Coulter et al, 2011). These cells represent a distinct subtype of interneurons that express both SST and PV (Maccaferri et al, 2000;Ferraguti et al, 2004), and their excitability was shown to be reduced in Dravet syndrome mice with global deletion of Na v 1.1 (Rubinstein et al, 2014).…”

β-Adrenergic modulation of spontaneous spatiotemporal activity patterns and synchrony in hyperexcitable hippocampal circuits

“…A combination of single-cell electrophysiology and fast imaging techniques (Carlson and Coulter 2008;Coulter et al 2011) can now allow us to probe the role of neuromodulators in altering neural activity patterns and intercellular synchronization (Dzirasa et al 2010;Fernandez de Sevilla et al 2006;Puig et al 2010). Thus it is important to use this combination of these techniques to determine emergent neural network dynamics and their modulation on cell-to-cell and network levels.…”

Emergence of functional subnetworks in layer 2/3 cortex induced by sequential spikes in vivo

“…During cortical circuit development in the mammalian brain, functional microcircuits form from groups of excitatory neurons receiving similar sensory information (33)(34)(35)(36)(37). The emergence of functional populations is not limited to the sensory cortex but also occurs in other subcortical areas during normal development or learning, a phenomenon that is increasingly acknowledged as a general characteristic of neural coding in the mammalian brain (38)(39)(40)(41)(42)(43). Presumably, changes in synaptic strength and/or modification of neuronal connectivity underlie this process, but we lack a systematic understanding of circuit rearrangement at a multineuron level.…”