The Influence of Amygdalo-Auditory Cortex Direct Projections in Audition and Tinnitus: An Optogenetic Reversible Deactivation Study

The role of the amygdalar projection to auditory cortex (AM-AC) is currently unknown. It has been hypothesized that AM-AC may help to manipulate descending control circuits for auditory attention. It could also serve a modulatory function in conjunction with the amygdalonucleus basalis-auditory cortex circuit to manipulate auditory conditioning and learning.

Methods (Experiment 1): To help elucidate the role of the direct amygdalo-auditory cortex pathway, optogenetic vectors (AAV-CaMKIIa-eNpHR3.0-EYFP) were placed into the amygdala of Long Evans rats to isolate and reversibly deactivate the pathway when a laser light was presented within auditory cortex. In the same animals, multichannel electrodes were implanted into auditory cortex. Auditory responses were then recorded from cortex in both normal and amygdalo-cortical light deactivation conditions.

In (Experiment 2), the role of the AM-AC in tinnitus perception was tested by inducing an acoustic tinnitus at the end of the surgery (see methods experiment 1 above). These animals were tested for their response to acoustic startle both with and without light deactivation of the circuit.

Results (Experiment 1): When the amygdalo-cortical circuit was deactivated with light, both single and multiunit activity was dramatically reduced for the duration of the light stimulation. However, the recording returned to normal levels immediately after the light was turned off. Experiment 2: Tinnitus behavior (a marked decrease in the startle versus gap acoustic reflex) was observed in the tinnitus induced animals. Light deactivation of the AM-AC caused the acoustic startle reflex to resembled the non-tinnitus behavior. The tinnitus behaviors immediately resumed when the light was turned off (i.e., AM-AC reactivation).

In both experiments, the location of the tracer was examined histologically after animals were euthanized. Results from these examinations revealed that the surgical locations for both recording and tracer injections were accurate. Examination of other brain regions revealed a few (very limited) neurons in the medial geniculate and nucleus basalis. Numerous labeled neurons were observed within the hippocampus.

Conclusions : The results from Experiment 1 indicate that the AM-AC has fairly profound but transient influences on cortical activity. This transient nature may indicate that it has a short-term modulatory influence on cortex to prime it for secondary circuits (e.g., amygdalonucleus basalis-auditory cortex).

While our results show that tinnitus was eliminated during deactivation of the pathway, the fact that deactivation had a profound influence on auditory activity during the recording experiments may indicate that the animals’; overall perception was reduced during activation which influenced the results.