Active avoidance is an intriguing learned behavior

The video shows a rat performing active avoidance.

When the light on the right side turns on (this is just for you ), the rat receives an innocuous sensory stimulus in its whisker pad that signals (for 7 sec) an upcoming mild foot-shock (if you put your finger tips on the grid, if feels like a tingling sensation).  In active avoidance, the subject predicts and controls the upcoming foot-shock. By moving to the other side of the cage during the presentation of the sensory stimulus, the foot-shock is avoided.  Before it was conditioned, the sensory stimulus produced no behavioral response because it had no meaning and was ignored.  After acquiring meaning (predicting the foot-shock), the sensory stimulus evokes a rapid avoidance response. This is fascinating and leads to many questions we are now able to tackle.

  • What neural circuits mediate active avoidance behavior?   
  • What changes in these circuits to code the significance of the sensory stimulus?  

During a normal day, we perform active and passive avoidance behaviors many times.  In some psychiatric disorders, such as anxiety disorders, subjects may avoid non-threatening events or situations, which can be highly problematic.  We are deciphering the neural circuits that mediate active avoidance. 

The video also shows how the state of the animal affects the sensory stimulus response evoked in the somatosensory cortex. More about this in the behavioral state page.  Continue reading below to learn some of the things we have discovered about active avoidance.

Active avoidance does not require the sensory thalamus

A surprising discovery  was that lesions of the somatosensory thalamus do no block the ability of the animals in response to a whisker pad stimulus (WCS, innocuous 10 Hz electrical stimulus delivered through a pair of subcutaneous wires).   The same result was obtained when animals trained to avoid to an auditory stimulus (ACS) received lesions of the auditory thalamus.  This indicates that the sensory thalamus and its targets (e.g. sensory cortex) are not required for active avoidance.

When the sensory thalamus is absent, due to a lesion, the superior colliculus in the midbrain fully mediates active avoidance

There is a neural correlate of active avoidance in superior colliculus

We recorded from cells in the superior colliculus during active avoidance and found that cells ramp up their activity during avoids.

The substantia nigra pars reticulata controls active avoidance

We discovered that modulating the firing of SNr cells controls active avoidance selectively (without affecting the ability of the animals to escape the footshock at these firing levels). Increases in SNr firing blocks avoidance, while decreases in SNr firing drives avoidance in the absence of the auditory stimulus (ACS).

Inhibition of the midbrain pedunculopontine tegmentum blocks signaled active avoidance

After finding that GABAergic SNr cells control signaled active avoidance, we tested the SNr pathways that control active avoidance. We discovered that activation of SNr pathways to the thalamus and superior colliculus do not suppress signaled active avoidance. Instead, projections from the SNr to the midbrain pedunculopontine tegmentum (PPT) control active avoidance. In fact, inhibiting excitatory cells in the PPT suffices to block signaled active avoidance. Conversely, excitation of local GABAergic neurons in PPT abolishes active avoidance.  Also, excitation of GABAergic afferents in PPT originating from SNr or zona incerta is sufficient to abolish signaled active avoidance. Moreover, excitation of excitatory neurons in PPT produces fleeing responses that can be tuned, in a frequency-dependent manner, to resemble fast escape responses (driven by the foot-shock) or slower avoidance responses (driven by the sensory stimulus that predicts the threat). The image below shows the effect of inhibiting CaMKII neurons in PPT with green light. Note the abolishment of signaled active avoidance at the higher green light powers.

SNr firing does not drive avoidance responses

Although the firing of SNr cells is modulated by avoidance responses, we discovered that SNr firing does not drive avoidance responses.  If we interfere with SNr activity, avoidance responses occur normally. The modulation of basal ganglia activity output via the SNr must serve another purpose other than driving avoidance responses. One possibility is that it serves to inform target structures about the ongoing response.