Cortical balance of excitation and inhibition is regulated by the rate of synaptic activity.

Taub AH, Katz Y, Lampl I.
J Neurosci. 2013 Sep 4;33(36):14359-68. PMID: 24005289

Objective:   Neurons are constantly integrating excitatory and inhibitory inputs transmitted by other cells.  These inputs increase or decrease during different brain states, and the cells themselves are able to regulate their own responses to the collective input.  How these balances shift can be counterintuitive and misunderstood.  In this paper, the authors examined the effect of light and deep anesthesia on excitatory and inhibitory inputs to cortical neurons and found that under deep anesthesia, presynaptic inhibitory cells are inhibited, which causes increases in the amplitude and duration of inhibitory neurotransmissions on the postsynaptic cell.

Results:

·         Under deep anesthesia, increased low-frequency EEG power was noted.  They also saw a decrease in EPSP and IPSP frequency.  However, they saw that the amplitudes and widths of IPSPs were larger, but those of EPSPs were not.

·         The altered characteristics could be due to presynaptic or postsynaptic changes.  The membrane characteristics of postsynaptic cells were examined and demonstrated no changes in resting potential or input resistance across levels of anesthesia.

·         These effects were not due to halothane, as rats given ketamine/halothane, propofol/halothane, propofol alone, and ketamine alone all showed the same effects.

·         Cells were examined for the recovery of spontaneous EPSPs and IPSPs after intracortical electrical stimulus trains.  They found that EPSPs recovered their amplitude and frequency faster than IPSPs, suggesting that a decrease in IPSP frequency could be responsible for the greater amplitude during anesthesia-induced inhibition.  They further investigated this observation by examining the envoked-IPSPs and found that there was an inverse correlation between stimulus frequency and IPSP amplitude, regardless of the level of anesthesia.

·         Methods:    4-8 week old rats were lightly or deeply anesthetized with halothane or halothane with propofol or ketamine and used for EEG recordings.  Whole-cell recordings were performed under current clamp with sufficient current applied to hold the cell at predesignated voltages which would enable clear observation of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs).  Cells were identified in vivo by well-established characteristics.  Electrical stimulations were performed with a tungsten electrode positioned just below the recording site.

-DH