On/Off Responses, Compact way to encode durration.

What is the best way to encode the duration of a sound with minimal expenditure of energy. Should a neuron be continuously on for the duration of the sound? Or can you just record the onset of the sound and the offset of the sound? As it turns out, a recent study by Dr. Haifu Li. et al, has shown that the primary auditory cortex (A1) can encode duration information with just the onset and offset of the sound. Furthermore, they are the first to show this in awake mice, by both recording neural activity in awake mice trained to detect the difference between the duration of sounds. And strikingly, they can even improve the rate at which the rats learn by manipulating certain neurons to boost the offset signal.

In A1 there are two relevant types of neurons, excitatory pyramidal neurons, and inhibitory PV neurons. Whenever a sounds starts, the pyramidal neurons fire shortly followed by the PV neurons. This results in a brief burst of spikes in the pyramidal neurons followed by silence. This is called the ON-response, shown in the above figure. Similarly, whenever the sound ends, the pyramidal neurons briefly fire, followed closely by the PV neurons. This is called the OFF-response.
 
To show that this mechanism encodes duration, they trained rats to distinguish between 300ms white noise sounds, and 50ms white noise sounds. As expected rats could easily learn to distinguish between the two sound stimuli after about 5 rounds. Then, when the researchers excited the PV neurons during the OFF-response, this completely quenched the OFF-response. As a result the trained animals no longer could perform the task.

However, the researchers did not stop there. In the course of their experiments, they noticed that the rats were worse at learning when the white noise stimuli was replaced with a single frequency tone. They also noticed, the OFF-response was weaker; less pyramidal neurons responded with a OFF-response to a single tone than the white noise. It would take more than double the time for the rats to learn the single tone discrimination task compared to the the white noise discrimination task.

Because the main difference between the stimuli was the response the magnitude of the Pyramidal neurons OFF-response, Dr. Li and collaborators reasoned that if they inhibited the PV neurons briefly during the OFF response, the OFF-response magnitude would be higher and the mice would learn better. Using a inhibitory optogenetic signal, they could momentarily suppress the PV neurons and boost the OFF-response. As predicted, the mice learned much faster with the PV neurons properly inhibited.

Perhaps even more impressively, the researchers where also able to train the mice without any sound. Now that they knew both ON-response and OFF-response where necessary and sufficient to calculate duration, they could use optogenetic stimulation to create artificial sounds only "heard" within the mice's auditory  cortex. Amazingly, once the mice learned with artificial sound, they were able to perform as well as the naturally trained mice when exposed to real sounds.

All these results conclusively prove that the brain using ON and OFF responses to efficiently encode sound duration. 


Author: Alexander White


Source: Haifu Li, Jian Wang, Guilong Liu, Jinfeng Xu, Weilong Huang, Changbao Song, Dijia Wang, Huizhong W. Tao, Li I. Zhang, Feixue Liang, Phasic Off responses of auditory cortex underlie perception of sound duration, https://doi.org/10.1016/j.celrep.2021.109003.

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