Abstract

Somatostatin-expressing, low threshold-spiking (LTS) cells and fast-spiking (FS) cells are two common subtypes of inhibitory neocortical interneuron. Excitatory synapses from regular-spiking (RS) pyramidal neurons to LTS cells strongly facilitate when activated repetitively, whereas RS-to-FS synapses depress. This suggests that LTS neurons may be especially relevant at high rate regimes and protect cortical circuits against over-excitation and seizures. However, the inhibitory synapses from LTS cells usually depress, which may reduce their effectiveness at high rates. We ask: by which mechanisms and at what firing rates do LTS neurons control the activity of cortical circuits responding to thalamic input, and how is control by LTS neurons different from that of FS neurons? We study rate models of circuits that include RS cells and LTS and FS inhibitory cells with short-term synaptic plasticity. LTS neurons shift the RS firing-rate vs. current curve to the right at high rates and reduce its slope at low rates; the LTS effect is delayed and prolonged. FS neurons always shift the curve to the right and affect RS firing transiently. In an RS-LTS-FS network, FS neurons reach a quiescent state if they receive weak input, LTS neurons are quiescent if RS neurons receive weak input, and both FS and RS populations are active if they both receive large inputs. In general, FS neurons tend to follow the spiking of RS neurons much more closely than LTS neurons. A novel type of facilitation-induced slow oscillations is observed above the LTS firing threshold with a frequency determined by the time scale of recovery from facilitation. To conclude, contrary to earlier proposals, LTS neurons affect the transient and steady state responses of cortical circuits over a range of firing rates, not only during the high rate regime; LTS neurons protect against over-activation about as well as FS neurons.

Highlights

  • Low threshold-spiking (LTS) neurons are a specific subtype of interneuron in the neocortex

  • It is thought that the activity of excitatory neurons is kept in check largely by inhibitory neurons; when such an inhibitory ‘‘brake’’ fails, a seizure can result

  • Using a computational model we show that, because the synaptic output of low threshold-spiking (LTS) neurons onto excitatory neurons depresses, the ability of LTS neurons to prevent strong cortical activity and seizures is not qualitatively larger than that of inhibitory neurons of another subtype, the fastspiking (FS) cells

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Summary

Introduction

Low threshold-spiking (LTS) neurons are a specific subtype of interneuron in the neocortex. Their somata are located in layers 2–6 [1], and they include the Martinotti cells of layer 5 [2,3,4,5] and the green fluorescent protein (GFP)-expressing neurons of the GIN line of transgenic mice [6,7,8]. The difference between the resting membrane potential and firing threshold of LTS cells is about 12 mV, smaller than observed in excitatory neurons or other types of inhibitory neurons [7]. LTS neurons are reciprocally coupled by depressing synapses to inhibitory neurons of the parvalbumin-expressing, fast-spiking (FS) type [10,14]. LTS neurons in layer 3 are excited by sensory inputs during whisking [17]), but these inputs could represent ascending layer 4-to-layer 3 excitation or neuromodulatory pathways

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