Simulations of cortical pyramidal neurons synchronized by inhibitory interneurons

W. W. Lytton, T. J. Sejnowski
<span title="">1991</span> <i title="American Physiological Society"> <a target="_blank" rel="noopener" href="" style="color: black;">Journal of Neurophysiology</a> </i> &nbsp;
AND CONCLUSIONS 1. The interaction between inhibitory interneurons and cortical pyramidal neurons was studied by use of computer simulations to test whether inhibitory interneurons could assist in phaselocking postsynaptic cells. Two models were used: a simplified model, which included only 3 membrane channels, and a detailed 1 l-channel model. 2. The 1 l-channel model included most of the ion channels known to be present in neocortical pyramidal neurons as well as calcium diffusion and other
more &raquo; ... mbrane mechanisms. The kinetics for the channels were obtained from voltage-clamp studies in a variety of preparations. The parameters were then adjusted to produce repetitive bursting similar to that seen in some cortical pyramidal cells entrained during visual stimulation. 3. Phase-locking to a train of inhibitory postsynaptic potentials (IPSPs) located on or near the soma was observed in the 3-channel model cell subjected to random synaptic bombardment. In the 1 l-channel model, phase-locking due to multiple IPSPs was compared with phase-locking due to multiple excitatory postsynaptic potentials (EPSPs). Phase-locking began to occur when 20% of the IPSPs (20/ 100) or 40% of the EPSPs (4,000/ 10,000) were synchronized. The exact percentages differed with different 1 i-channel models, but either EPSPs or IPSPs would generally produce entrainment with ~40% synchronization. Thus 40 inhibitory boutons had an effect equivalent to 4,000 excitatory boutons in producing phase-locking. 4. Phase-locking with IPSPs in these models was possible because the IPSPs could cause either an increase or a decrease in firing rate over a limited range. The IPSPs served a modulatory role, increasing the rate of firing in some cases and decreasing it in others, depending on the state of the cell. 5. We examined frequency entrainment by IPSPs. In the 3channel model, frequency entrainment of a postsynaptic cell was observed with a rapid train of strong (20-100 nS), brief, compound IPSPs. A 40-Hz compound IPSP train of 60 nS entrained cells having initial firing rates between 32 and 47 Hz. Below this range, cells could be partially entrained. Above the range, entrainment would fail. Frequency entrainment in the 3-channel model generally occurred on the first cycle after onset of the IPSPs. 6. Phase-locking and frequency entrainment were less robust in the 1 l-channel model. This was partly because bursts rather than individual spikes were being entrained. A 40.Hz, 90-nS compound IPSP train entrained a model cell upward from 34 Hz. Downward frequency entrainment also occurred. In the 1 l-channel model entrainment usually occurred on the second cycle after onset of the IPSPs. 7. Downward frequency entrainment was due to the direct effects of inhibition in delaying firing of the cell.The occurrence of upward frequency entrainment was more surprising and was studied in detail. The upward entrainment observed in the 3-channel model occurred because hyperpolarization turned off a slow potassium channel, making subsequent firing more likely. Acceleration from low to higher frequency also occurred in the 1 l-channel model, but was due to a different mechanism. The IPSPs reduced the burst size and allowed less calcium to enter the cell, which reduced the interburst hyperpolarization mediated by a Ca2+-sensitive K+ current. The occurrence of IPSP frequency entrainment by distinctly different mechanisms in these different models suggests that the phenomenon might occur in a variety of cells. 8. The large conductances needed to obtain phase-locking in our simulations could be produced by the coordinated firing of six to eight inhibitory basket cells making multiple synaptic contacts onto somas or proximal apical dendrites of pyramidal neurons. In both models, IPSP phase-locking was shown to be effective with the use of shunting inhibition with the IPSP located on the proximal dendrite. Therefore y-aminobutyric acid-A synapses could be involved. In the 3-channel model we also showed phase-locking by the use of synapses onto the axon initial segment. This suggests that chandelier cells could also play a role in phase-locking. 9. IPSP entrainment could contribute to the phase-locking observed in visual cortex. Support for this comes from previous reports of brief, rapid IPSP trains at optimal stimulation of orientation-tuned cells in visual cortex.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.1152/jn.1991.66.3.1059</a> <a target="_blank" rel="external noopener" href="">pmid:1661324</a> <a target="_blank" rel="external noopener" href="">fatcat:la6hufecvbb65c62gmv5uvk7jy</a> </span>
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