Different temporal processing of sensory inputs in the rat thalamus during quiescent and information processing states in vivo

Abstract

Sensory inputs from the whiskers reach the primary somatosensory thalamus through the medial lemniscus tract. The main role of the thalamus is to relay these sensory inputs to the neocortex according to the regulations dictated by behavioural state. Intracellular recordings in urethane-anaesthetized rats show that whisker stimulation evokes EPSP-IPSP sequences in thalamic neurons. Both EPSPs and IPSPs depress with repetitive whisker stimulation at frequencies above 2 Hz. Single-unit recordings reveal that during quiescent states thalamic responses to repetitive whisker stimulation are suppressed at frequencies above 2 Hz, so that only low-frequency sensory stimulation is relayed to the neocortex. In contrast, during activated states, induced by stimulation of the brainstem reticular formation or application of acetylcholine in the thalamus, high-frequency whisker stimulation at up to 40 Hz is relayed to the neocortex. Sensory suppression is caused by the depression of lemniscal EPSPs in relatively hyperpolarized thalamocortical neurons. Sensory suppression is abolished during activated states because thalamocortical neurons depolarize and the depressed lemniscal EPSPs are able to reach firing threshold. Strong IPSPs may also contribute to sensory suppression by hyperpolarizing thalamocortical neurons, but during activated states IPSPs are strongly reduced altogether. The results indicate that the synaptic depression of lemniscal EPSPs and the level of depolarization of thalamocortical neurons work together in thalamic primary sensory pathways to suppress high-frequency sensory inputs during non-activated (quiescent) states while permitting the faithful relay of high-frequency sensory information during activated (processing) states.

Figure 1. Intracellular correlates of whisker-evoked responses in VPM neurons

A, example of a typical EPSP induced by whisker stimulation and its depression by a second stimulus delivered 100 ms later. Notice the fast rise and large amplitude of the evoked response and the strong synaptic depression of the second response (right panel). Below is the effect of seven sensory stimuli delivered at 10 Hz. Notice that the degree of synaptic depression is constant after the third stimulus. The neuron was hyperpolarized to about −80 mV using −0.5 nA current injection. B, sensory-evoked EPSPs are followed by IPSPs, which themselves depress with repetition. Notice that despite the strong depression of IPSPs the EPSP also remains depressed, indicating that EPSP depression was not due to strong inhibition. The neuron was at resting potential. C, sensory-evoked responses in some VPM neurons consist of IPSPs alone. Notice the robust IPSPs and their frequency-dependent depression. Intracellular recordings were performed using K⁺-filled pipettes. The AC-coupled square pulses on the traces mark the whisker stimuli.

Figure 2. Frequency-dependent depression of whisker-evoked EPSPs in VPM neurons

A, application of whisker stimulation at 40, 20, 10 and 5 Hz depresses thalamic EPSPs. Traces are the average of 3-5 trials. The cell was hyperpolarized to −81 mV with current injection (-0.5 nA). B, overlaid are the first (1) and fifth (2) evoked responses for the 10 Hz stimulus train shown in A (left panel). From the same recording four spontaneously occurring large amplitude events are shown, which presumably correspond to spontaneous activity in lemniscal afferents (middle panel). An overlay between the sensory-evoked response to the first stimulus and a spontaneous event reveals a close fit, which suggests that the evoked response is composed of two spontaneous events.

Figure 3. Effect of thalamic activation induced by RF stimulation on whisker-evoked responses in VPM neurons

A, RF stimulation (100 Hz, 1 s) induces thalamic activation which was monitored by field potential (above) and single-unit recordings (below) using the same electrode placed in the VPM thalamus. B, the effect of four whisker stimuli (1 ms pulses) delivered at 20 Hz and at 2 Hz is shown as a raw trace for one trial (above) and as the binned sum of 14 trials (below). C, the response to the same whisker stimulation as in B is displayed during thalamic activation induced by RF stimulation. The 1 ms positive square pulses on the raw traces mark the time of the sensory stimulus. Notice that the x-axis for the 2 Hz stimulation is not continuous.

Figure 4. Spectrum analysis of whisker-evoked responses during quiescent and activated states in VPM neurons

A, the probability of single-unit firing for 10-20 stimulus trials during the 3-6 ms time window after the whisker stimulation is displayed. The average response to four stimuli delivered at 1, 2, 5, 10, 20 and 40 Hz is shown for five single units during quiescent conditions (control) and during thalamic activation caused by RF stimulation. B, a spectrum analysis was performed during control conditions and during thalamic activation using the fourth response of the stimulus train. The average firing probability to the fourth stimulus for each frequency is displayed. The data correspond to the mean ± s.d. of five experiments.

Figure 5. Effect of acetylcholine on whisker-evoked responses in a VPM neuron

Single-unit response to whisker stimulation displayed as the binned (2 ms bins) sum of 30 trials each consisting of 15 whisker stimuli delivered at 40 Hz (left panels), 20 Hz (middle) and 10 Hz (right), before (upper panels), during (middle) and after (lower) application of acetylcholine to VPM. Notice that the single unit responds to whisker stimulation at up to 40 Hz during acetylcholine application, but not before or after. The first stimulus is delivered at time zero.

Figure 6. Population data on the effect of acetylcholine on whisker-evoked responses in VPM neurons

A, mean counts of seven single units displayed as the binned (2 ms bins) sum of 30 trials each consisting of 15 whisker stimuli delivered at 40 Hz (left panels), 20 Hz (middle) and 10 Hz (right), before (upper panels) and during (lower) application of acetylcholine to VPM. B, spectrum analysis of whisker-evoked responses in VPM neurons before and during the application of acetylcholine. The average firing probability to 30 trials during the 3-7 ms time window after the 15th stimulus is displayed for each frequency. The data correspond to the mean ± s.d. of seven experiments.

Figure 7. Postsynaptic depolarization can eliminate thalamic sensory suppression

Intracellular recording from a VPM neuron responding to whisker stimulation. When the neuron is at resting membrane potential (around−65 mV) and four stimuli are applied at 10 Hz, the neuron only responds with an action potential to the first stimulus. However, when the neuron is depolarized by 10 mV the whisker stimulation is effective at driving the neuron at 10 Hz. Shown are also the sensory responses at membrane potentials hyperpolarized using current injection. Applied DC curents were: 0.4, 0, −0.2, −0.7 and −1.4 nA (top to bottom traces). Action potentials are truncated.

Figure 8. Robust whisker-evoked IPSPs can restrict the ability of postsynaptic depolarization to eliminate thalamic sensory suppression

A, intracellular recording from a VPM neuron that responds to whisker stimulation with an EPSP followed by a robust IPSP. Both the EPSPs and IPSPs depress with repetition at 10 Hz (right panel). B, when sensory-evoked IPSPs are very robust, postsynaptic depolarization is not effective in eliminating thalamic suppression during the initial stimulus trials when inhibition has not yet depressed. Notice that at resting potential (0 DC) the cell only produces an action potential to the first stimulus, and despite strong depression of IPSPs there is no relay of sensory inputs during the latter stimuli. As the neuron is depolarized from resting the latter stimuli are able to relay the sensory input, but the initial stimuli are not capable because of the strong sensory-evoked IPSPs. Whisker stimulation consisted of 15 stimuli at 10 Hz. Action potentials are truncated.

Figure 9. Whisker-evoked IPSPs are suppressed by thalamic activation

A, example of an intracellular recording from a VPM neuron showing the effect of stimulating the brainstem reticular formation (100 Hz, 1 s). The right trace is a close-up. B, the neuron responded to whisker stimulation (15 stimuli, 10 Hz) with robust IPSPs that hyperpolarized the cell during the initial sensory stimuli (control). Thalamic activation produced by stimulating the brainstem reticular formation blocked the sensory-evoked IPSPs in the VPM neuron (RF). Action potentials are truncated. C, IPSP evoked by a single whisker stimulus delivered before (Control) and after RF stimulation. Both traces are overlaid for comparison. The membrane potential values for the beginning of each trace (before the whisker stimulus) are displayed.

Figure 10. Effect of disinhibition and subsequent muscarinic receptor block on whisker-evoked responses in VPM neurons

Single-unit response in VPM to whisker stimulation displayed as the binned (2 ms bins) sum of 30 trials each consisting of 15 whisker stimuli delivered at 40 Hz (left panels), 20 Hz (middle) and 10 Hz (right), before (upper panels) and during the application of BMI and CGP35348 (middle) and during the application of BMI, CGP35348 and scopolamine (lower) to VPM. Notice that the single unit responds to whisker stimulation at up to 40 Hz during disinhibition produced by BMI and CGP35348, but that this effect is eliminated by the muscarinic antagonist scopolamine.