Neocortical Network ActivityIn VivoIs Generated through a Dynamic Balance of Excitation and Inhibition

Abstract

The recurrent excitatory and inhibitory connections between and within layers of the cerebral cortex are fundamental to the operation of local cortical circuits. Models of cortical function often assume that recurrent excitation and inhibition are balanced, and we recently demonstrated that spontaneous network activity in vitro contains a precise balance of excitation and inhibition; however, the existence of a balance between excitation and inhibition in the intact and spontaneously active cerebral cortex has not been directly tested. We examined this hypothesis in the prefrontal cortex in vivo, during the slow (Ͻ1 Hz) oscillation in ketamine-xylazine-anesthetized ferrets. We measured persistent network activity (Up states) with extracellular multiple unit and local field potential recording, while simultaneously recording synaptic currents in nearby cells. We determined the reversal potential and conductance change over time during Up states and found that the body of Up state activity exhibited a steady reversal potential (Ϫ37 mV on average) for hundreds of milliseconds, even during substantial (21 nS on average) changes in membrane conductance. Furthermore, we found that both the initial and final segments of the Up state were characterized by significantly more depolarized reversal potentials and concomitant increases in excitatory conductance, compared with the stable middle portions of Up states. This ongoing temporal evolution between excitation and inhibition, which exhibits remarkable proportionality within and across neurons in active local networks, may allow for rapid transitions between relatively stable network states, permitting the modulation of neuronal responsiveness in a behaviorally relevant manner.

GABAergic Excitation in the Basolateral Amygdala

“…Given that these strong connections are clustered, and the highly nonrandom nature of synaptic connectivity, it is conceivable that pyramidal neurons with strong connections may be the recipient of suprathreshold AAC excitation. This provides an ideal mechanism for the rapid activation of large numbers of pyramidal neurons, as occurs in the transition from a hyperpolarized network Down state to the depolarized Up state (Steriade et al, 1993;Cossart et al, 2003;Haider et al, 2006), a phenomenon that has been observed not only in the cortex but also in the amygdala (Collins et al, 2001).…”

What we can do and what we cannot do with fMRI

“…Alternating up states and down states can be readily observed in cerebral cortex during natural sleep or anaesthesia 30 , but they can be also induced in vitro by manipulating the ionic concentrations in a preparation so that they match those found in situ. Research showed that the up state is characterized by persisting synaptically mediated depolarization of the cell membranes owing to strong barrages of synaptic potentials, and a concomitant increase in spiking rate, whereas the down state is marked by membrane hyperpolarization and reduction or cessation of firing 31,32 . Most importantly, the excitation-inhibition conductances indeed changed proportionally throughout the duration of the up state despite large changes in membrane conductance 31,32 .…”

Dysfunction of hippocampal interneurons in epilepsy

“…Because the majority of interneurons synthesize and release γ-amino-butyric acid (GABA), they are also referred to as GABAergic or inhibitory interneurons [1] . The balance between excitation and inhibition is crucial, and the maintenance of dynamic equilibrium involves many physiological mechanisms [3] .…”