Increased synaptic noise induces multiplicative gain changes.

<p><b>A and B</b>. Bath-application of 250 µM trans-ACPD increased the standard deviation of the membrane potential in TC cells. Note the large increase in activity centred around baseline (dashed line, -67 mV) in A. The increase in SD is comparable to the highest level of current noise (1.57 vs 1.6 ). <b>C</b>. For each individual cell (n  =  3) bath application of trans-ACPD increased gain in comparison to control. The increase in gain was paralleled by a reduction in the amplitude of the sAHP (<b>D</b>; main panel and inset).</p

Noise normalises gain changes.

<p><b>A</b>. Gain changes were not uniform within the recorded population, as noise reduced gain in cells with initially high gains (n  =  5, open circles), and increased gain in those with low initial gains (n  =  13, closed circles). <b>B.</b> Histograms of gains across the sample population (n  =  18) under control conditions (dashed line) and for the highest level of noise (σ₅₀, solid line). Note the sharper distribution of gains under noisy conditions. <b>C</b>. The standard deviation of the average of gains across the population, plotted against the corresponding noise level. The standard deviation is reduced by 52% at high noise levels. Data were fit with an inverse exponential function.</p

TC cells display a wide range of gains and thresholds.

<p><b>A</b>. Firing rate as a function of input current amplitude (f-I relationship) for a typical TC cell. A straight line was fitted from the first point above tonic firing threshold to the last recorded response; the slope of this fit was a measure of gain. The gain and threshold of this neuron were 0.432 Hz/pA and 180 pA respectively. Shown to the right are representative traces recorded in response to 200, 300 and 400 pA (square, diamond, and circle respectively) current pulses. <b>B</b>. Firing threshold plotted as a function of gain. Both measures were normalised against the input resistance of each cell to minimize error associated with cell soma area. The average of each measure (and their respective SEMs) is indicated by the empty circle. A histogram of normalised gain (above) demonstrates that gains are normally distributed.</p

T-type Ca²⁺ channel block induces additive and multiplicative gain changes.

<p><b>A</b>. Graph plotting the increase in gain during bath-application of 250 µM Ni²⁺ for each recorded cell. <b>B</b>. As in <b>A</b>., with sAHP plotted for each cell.</p

Burst and tonic spikes occur within exclusive temporal domains.

<p><b>A</b>. The stereotypical response of a TC cell to a 1s, 200 pA depolarising current pulse delivered from resting membrane potential (-65 mV). The onset of the response (first 150 ms, inset) is characterised by a high frequency burst of spikes (246 Hz, arrow) followed by a shift to tonic firing. <b>B</b> . Interspike interval (i.s.i.) histogram (1 ms bin width) from a single TC cell in the response to a set of 20 current steps from 0 to 400 pA. Note the clear segregation either side of the 5 ms interval. Adjacent spikes with intervals shorter than 5 ms were classified as “burst” spikes, while those greater than 5 ms were classified as “tonic” spikes. Intervals greater than 50 ms (4 out of 693 in this example) were excluded from the plot for clarity.</p

Schematic of the mouse dorsal lateral geniculate nucleus (dLGN) and representative noise stimuli.

<p><b>A</b>. The dLGN is shown in relation the hippocampus (CA3 and CA1), ventral lateral geniculate nucleus (vLGN), lateral posterior nucleus (LP), posterior nucleus (PO), and the medial portion of the posterior nucleus (VPM) in a coronal plane (2.06 mm caudal to Bregma, left hemisphere). Inset shows the map of recording sites within the dLGN. Note that cells were recorded throughout the dorsoventral, and mediolateral extent of the LGN (Plates 45–51 in Paxinos and Watson, 2008. On the bottom right is a photo of a representative TC neuron. <b>B</b>. The response of a cell to a noisy current stimulus with a mean current of 0 pA. The value σ_12.5 for current noise of different standard deviations (n) was calculated as the standard deviation of the recorded membrane potential. The noise levels presented throughout are the average of the standard deviation (caused by this stimulus for each n) across all cells tested.</p

Noise induces both additive and multiplicative gain changes

<p><b>A</b>. Shows for a typical TC cell the f-I relationships plotted at different levels of current noise (σ_n, where σ is the standard deviation of the membrane potential in response to a ‘noisy’ current pulse with a mean current of 0 pA, and n represents the standard deviation of the injected current noise). In this example, the highest level of noise significantly increased the gain (0.05 to 0.39 Hz/pA; multiplicative gain change, indicated by an increase in the slope) and decreased the threshold (160 to 140 pA; additive gain change, indicated by a shift to the left) of this cell in comparison to control conditions. <b>B</b>. Gains averaged across the sample population plotted against noise level. On average, increasing levels of noise increased the gain of TC cells. Data points were well fit by an inverse exponential function, indicating that increases in gain saturate at high noise levels. <b>C</b>. Increasing levels of noise reduced the threshold of TC cells. As in B, this reduction saturated at high noise levels (between 1.0 and 1.5).</p

Discharge profiles of spontaneous and non-spontaneous EVN neurons.

<p><b>(A)</b> Schematic view of transversely sectioned mouse brainstem. Inset shows map of recording sites from a subset of EVN neurons (37/54 recorded neurons). <i>VN</i>: vestibular nucleus; <i>G7n</i>: genu of seventh cranial nerve (facial nerve); <i>6n</i>: sixth cranial nerve nucleus (abducens nucleus); <i>4V</i>: fourth ventricle; <i>EVN</i>: efferent vestibular nucleus. <b>(B)</b> EVN neurons are either spontaneous firing (<i>n</i> = 16) (<i>top trace</i>) or non-spontaneously firing (<i>n</i> = 38) (<i>bottom</i> trace) at resting membrane potential and display homogenous discharge profiles in response to depolarizing <b>(C)</b> and hyperpolarizing <b>(E)</b> step currents. EVN neurons respond with a short burst (*) of high frequency action potentials (AP) at the onset of a depolarizing stimulus or the cessation of a hyperpolarizing stimulus. <b>(D)</b> Comparison of instantaneous frequencies as a function of injected depolarizing current from a subset of MVN and EVN neurons from which the slope of linear fit was used to calculate the gain of each neuron. *** <i>p</i><0.001. <b>(F)</b> EVN neurons displayed an afterdepolarization (ADP) following release from inhibition (arrow in <b>(E)</b>). The ADP was mediated by T-type calcium channels—TTX (1 μM) abolished all APs, and TTA-P2 (1 μM) abolished the remaining response.</p

EPSC and mIPSC properties.

<p><b>(A)</b> AMPA/kainate type glutamate receptor, GABA_AR and GlyR-mediated EPSCs and mIPSCs. <b>(B)</b> Averaged GABA_AR- and GlyR- mediated mIPSCs, and AMPA/kainate glutamate receptor mediated EPSC, isolated from the recordings shown above. <b>(C)</b> Bar graphs showing GABA_AR-, GlyR-mediated mIPSCs and AMPA/kainate glutamate receptor mediated EPSC amplitude, decay time, rise time, and width. * <i>p</i><0.05, ** <i>p</i><0.01. Values within bars indicate the number of cells sampled. Double diagonal lines indicate that EPSC and mIPSCs values are not compared, but are presented on same bar graph for ease of demonstration.</p

Identification and classification of excitatory and inhibitory profiles in EVN neurons.

<p><b>(A)</b> Schematic view of transversely sectioned mouse brainstem. Inset shows map of recording sites (22/23 recorded neurons). <i>VN</i>: vestibular nucleus; <i>G7n</i>: genu of seventh cranial nerve (facial nerve); <i>6n</i>: sixth cranial nerve nucleus (abducens nucleus); <i>4V</i>: fourth ventricle; <i>EVN</i>: efferent vestibular nucleus. <b>(B)</b><i>Top trace</i>: EPSCs recorded under normal conditions before the addition of drugs. <i>Second trace</i>: addition of CNQX (10 μM) and TTX (1 μM). <i>Third trace</i>: mIPSCs recorded under normal conditions before the addition of drugs. <i>Bottom trace</i>: addition of strychnine (1 μM) and bicuculline (10 μM) abolished all synaptic activity. Some neurons received excitatory inputs in conjunction with: GABA_AR-mediated events <b>(C)</b><i>Bottom trace</i>: addition of bicuculline to the bath abolished activity remaining after the addition of TTX and CNQX (<i>second trace</i>); GlyR-mediated events <b>(D)</b><i>Bottom trace</i>: addition of strychnine abolished remaining activity following the addition of TTX and CNQX (<i>second trace</i>). <b>(E)</b> Other neurons received a combination of mIPSCs in addition to EPSCs. In these neurons, the addition of bicuculline reduced the frequency of synaptic activity (<i>third trace</i>) that was abolished by addition of strychnine (<i>bottom trace</i>). Scale bar in <b>(B)</b> is the same for all traces. <b>(F)</b> Frequencies of EPSCs and mIPSCs per cell calculated over a period of 30 seconds under the influence of excitatory and inhibitory synaptic activity blockers.</p