Heterosynaptic plasticity of the visuo-auditory projection requires cholecystokinin released from entorhinal cortex afferents.

The entorhinal cortex is involved in establishing enduring visuo-auditory associative memory in the neocortex. Here we explored the mechanisms underlying this synaptic plasticity related to projections from the visual and entorhinal cortices to the auditory cortex in mice using optogenetics of dual pathways. High-frequency laser stimulation (HFS laser) of the visuo-auditory projection did not induce long-term potentiation. However, after pairing with sound stimulus, the visuo-auditory inputs were potentiated following either infusion of cholecystokinin (CCK) or HFS laser of the entorhino-auditory CCK-expressing projection. Combining retrograde tracing and RNAscope in situ hybridization, we show that Cck expression is higher in entorhinal cortex neurons projecting to the auditory cortex than in those originating from the visual cortex. In the presence of CCK, potentiation in the neocortex occurred when the presynaptic input arrived 200 ms before postsynaptic firing, even after just five trials of pairing. Behaviorally, inactivation of the CCK+ projection from the entorhinal cortex to the auditory cortex blocked the formation of visuo-auditory associative memory. Our results indicate that neocortical visuo-auditory association is formed through heterosynaptic plasticity, which depends on release of CCK in the neocortex mostly from entorhinal afferents.

Pulsed infrared stimulation evoked electrical potential in mouse vestibular system.

To improve accuracy of VsEP and avoid the inherent limitation of mechanical vibration, we designed an infrared optical stimulation approach to stimulate mouse vestibular system and measured the evoked potential. IR pulses (1871 nm, 30 pps and 100 µs pulse width) were delivered to mice with different vestibular dysfunction levels and the evoked potential was recorded. The result suggests that the amplitude and latency of the IR-evoked potential (IR-VsEP) were significantly associated with vestibular function integrity. Immunofluorescence staining confirmed that magnitude of IR-VsEP decreased was consistent with the loss of HCs. Micro-CT imaging revealed that the optical fiber was orientating towards the vestibular system. Taken together, we found that: 1) IR stimulation can generate VsEP evoked potential in vestibular system (IR-VsEP), which can be potentially used for vestibular function evaluation; 2) intact HCs and fully functional synaptic transmission are crucial for efficient IR-induced vestibular system stimulation.