Waking and vigilance suppress sensory responses in the neocortex
The image below shows an experiment in which we recorded field potential responses in the somatosensory (barrel) cortex of a freely moving rat evoked by stimulating the thalamocortical pathway. We discovered that the thalamocortical evoked response is suppressed (reduced) when the animal is awake compared to when it is sleeping (slow-wave sleep). This was neither known nor expected at the time. Panel B shows the amplitude of the evoked response measured every few seconds (black circles are a running average of the red circles). The other panels serve to characterize the state of the animal. During the initial 10 minutes, the animal is sleeping rolled up in a corner of the cage (slow oscillations 1-2 Hz are evident in the power spectrum in panel A, there is no motor activity measured with photobeams and the whisker pad EMG is flat). Shortly after, the animal spontaneously wakes up (as evidenced by motor activity, whisking EMG, and power spectrum). Intriguingly, the evoked thalamocortical response is much smaller when the animal is awake compared to sleep. The red circles also show that there is significant variability during both states.
Sensory suppression in the anesthetized brain
We also found that stimulating the brainstem reticular formation (BRF), which awakes the anesthetized brain, produced the same effect as natural waking; sensory (whisker) responses evoked in the barrel cortex are suppressed. The image below shows this by recording field potentials, single-units, current-source densities, and intracellular responses evoked before and after BRF stimulation. Responses become suppressed and less variable.
Sensory suppression serves to focus receptive fields
The intriguing finding that sensory responses are suppressed during waking, or BRF stimulation, leads to the obvious question: why? We found that sensory suppression is useful to focus receptive fields and sensory representations. The image shows a 16-ch silicon probe placed horizontally in layer IV to record sensory responses evoked by deflecting a single whisker. BRF stimulation suppresses the spread of cortical activity so that the representation becomes more circumscribed to a single barrel. This should be useful for discrimination.
Sensory suppression during complex behavior reflects state changes
We discovered that sensory suppression indeed occurs during complex behavior for the conditioned stimulus being detected and this leads to changes in frequency-dependent adaptation. Importantly, the suppression is related to the state of vigilance and not the learning per se. The video shows a field potential recording in the whisker region of the somatosensory cortex (barrel cortex) during active avoidance behavior.
The overlaid traces correspond to the first 10 stimuli of the 10 Hz train that signals the footshock. When the animal is learning, the cortical evoked responses are small and similar to each other (there is little sensory adaptation). However, when the animal has performed many trials (2nd part of the video), the response becomes very large to the 1st stimulus in the 10 Hz train and it depresses for subsequent stimuli (it shows much more sensory adaptation). This is not caused by learning, but by the state of the animal. Note that when the cortical evoked responses are small, the animal is very alert. When the evoked responses are large, the animal is quiescent (~taking a nap). Neural circuits change their response properties during different behavioral states to allow adequate information processing as behavioral contingencies demand. This also shows that when animals are well-trained and can both predict and control the threat, they show little evidence of fear (napping ≠ fear).
Sensory suppression is caused by thalamocortical activity
Every time we caused sensory suppression, thalamocortical cells would fire at high rates. Since thalamocortical responses evoked in the cortex are known to depress with activity, we reasoned that sensory suppression might be the result of direct thalamocortical firing. To test this idea, we monitored thalamocortical responses evoked by stimulating the thalamic radiation (thalamocortical fibers coursing to the cortex). BRF stimulation suppressed these thalamocortical evoked responses. But when we blocked thalamocortical firing within the thalamus (with TTX), the sensory suppression caused by BRF stimulation was abolished indicating that the increase in thalamocortical firing caused by BRF stimulation was causing the sensory suppression. Thus, increases in thalamocortical firing (VPM cells in somatosensory thalamus) caused by changes in the behavioral state lead to the suppression of sensory-evoked responses in barrel cortex.
Increasing thalamocortical activity suffices to produce sensory suppression
We found that solely increasing the firing of thalamocortical cells produces sensory suppression. [CA, cholinergic agonist (carbachol)]
Thalamocortical activity activates (awakes) the cortex
We noticed that every time the thalamus increased its firing spontaneously, the cortex would show signs of “activation”. During activation, slow cortical oscillations (typical of slow-wave sleep) are abolished. In essence, the cortex wakes up. This led us to test the idea that thalamocortical firing might be able to cause cortical activation. We discovered that by controlling the firing of thalamocortical cells in the somatosensory thalamus, we could control the state of the related somatosensory cortex. Moreover, we performed this control by applying neuromodulators into the somatosensory thalamus, which provides a feasible mechanism for how this may occur normally.
[CA, cholinergic agonist; NE, norepinephrine]
Thalamocortical neurons in the sensory thalamus are also sensitive to behavioral state but their responsiveness is enhanced, not suppressed
This is well exemplified by the following video. In this anesthetized preparation (slow oscillation mode) the state of the thalamus is controlled by stimulating the brainstem reticular formation (activated mode); basically the sleeping thalamus is briefly woken up so the sensory responses can be compared in both states. We discovered that state affects primarily the responsiveness of high frequency sensory inputs, which are blocked during the slow oscillation mode, but allowed during the activated mode. The panels shows a single-unit recording in the VPM thalamus evoked by a whisker deflection at either 0.1 or 10 Hz. Note that during the oscillation mode the neuron only responds to the low frequency whisker deflections, but during the activated mode it responds to both the low and high frequency whisker deflections. The small responses visible when the large spike fails are the “s” potentials (synaptic); the synaptic potentials viewed from the extracellular space, which are unable to reach spike firing threshold in the slow oscillation mode.
The superior colliculus is highly sensitive to state changes
Recording from the superior colliculus in freely moving rats we discovered that cells change their activity quite a bit depending on the behavioral state. This is shown in the following image. Note how the firing of the recorded cell varies depending on what the animal is doing and as the animal transitions between states. [SWS, slow-wave sleep; AWIM, awake-immobile; ACEX, active exploration]