Synaptic Contributions to Focal and Widespread Spatiotemporal Dynamics in the Isolated Rat SubiculumIn Vitro

Abstract

The subiculum, which has a strategic position in controlling hippocampal activity, is receiving significant attention in epilepsy research. However, the functional organization of subicular circuits remains unknown. Here, we combined different recording and analytical methods to study focal and widespread population activity in the isolated subiculum in zero Mg 2ϩ media. Patch and field recordings were combined to examine the contribution of different cell types to population activity. The properties of cells leading field activity were examined. Predictive factors for a cell to behave as leader included exhibiting the bursting phenotype, displaying a low firing threshold, and having more distal apical dendrites. A subset of bursting cells constituted the first glutamatergic type that led a recruitment process that subsequently activated additional excitatory as well as inhibitory cells. This defined a sequence of synaptic excitation and inhibition that was studied by measuring the associated conductance changes and the evolution of the composite reversal potential. It is shown that inhibition was time-locked to excitation, which shunted excitatory inputs and suppressed firing during focal activity. This was recorded extracellularly as a multi-unit ensemble of active cells, the spatial boundaries of which were controlled by inhibition in contrast to widespread epileptiform activity. Focal activity was not dependent on the preparation or the developmental state because it was also recorded under 5 mM [K ϩ ] o and in adult tissue. Our data indicate that the subicular networks can be spontaneously organized as leader-follower local circuits in which excitation is mainly driven by a subset of bursting cells and inhibition controls spatiotemporal firing.

Extracellular Calcium Controls the Expression of Two Different Forms of Ripple-Like Hippocampal Oscillations

“…Previous data show that activation curves of persistent Na ϩ channels shift to more negative potentials at 1 mM Ca 2ϩ (Su et al, 2001;Yue et al, 2005). These currents contribute to spike afterdepolarization that cause neurons to burst (Azouz et al, 1996;Menendez de la Prida et al, 2003), thus rendering cells hyperexcitable. Altogether, these data suggest profound effects of extracellular Ca 2ϩ on intrinsic excitability.…”

Conundrums of High-Frequency Oscillations (80–800 Hz) in the Epileptic Brain

“…In the intact brain, propagation of HFO-associated excitatory bouts of activity through the parahippocampal synaptic pathway is typically constrained by region-specific recruitment of fast inhibitory circuits (Menendez de la Prida and Pozo, 2002; Menendez de la Prida and Gal, 2004). Thalamic activation of neocortical territories is temporally controlled by feedforward and feedback local inhibition (Swadlow et al 2005).…”

The subiculum comes of age

“…The combination of an effective recurrent inhibition and low threshold burst firing cells, which exert strong recurrent excitatory actions on their neighbors, may ensure that specific subicular pyramidal cells can participate in different ensembles in response to distinct afferent signals. In vitro data supports this model of subicular function (Menendez de la Prida and Gal, 2004). The temporal persistence of representations, apparent in vivo, implies that spatial information must be transferred from the subiculum to circuits that can sustain tonic firing, such as the EC (Egorov et al, 2002), before it re-enters the subicular loop to maintain spatial coding.…”

“…Certainly, in isolated slice preparations, the subiculum generates several distinct forms of synchronous activity (Behr and Heinemann, 1996). In vitro data also shows that low threshold, burst firing subicular pyramidal cells can recruit other glutamatergic cells and GABAergic interneurons to population burst firing (Harris and Stewart, 2001b;Menendez de la Prida and Gal, 2004). Subicular interneurons may have an especially important role.…”