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Mapping the neuronal representation in dorsal inferior colliculus through optical imaging, stimulus optimization and optogenetics

Periodic Reporting for period 1 - OPTIMAPIC (Mapping the neuronal representation in dorsal inferior colliculus through optical imaging, stimulus optimization and optogenetics)

Reporting period: 2015-03-01 to 2017-02-28

Even though it is the most accessible subcortical auditory structure, remarkably little is known about the dorsal cortex (ICd) of the inferior colliculus. In contrast to the well-studied central nucleus, we have yet to discover any functional organization in ICd, and there is little short-distance local connectivity among ICd neurons. Moreover, except for a recent study, these experiments have been performed in anaesthetized animals, where inputs from neocortex are thought to be perturbed.

Understanding the normal function of the auditory system is vital to the treatment of auditory disorders such as hearing loss and tinnitus. The Optimapic project aimed to get a more thorough understanding of the functional organization of the ICd, by combining numerous state-of-the-art techniques such as in vivo calcium imaging, operant conditioning, optogenetics and a stimulus optimization approach.

The three main objectives are:
1. Understand the basic neural code in ICd through stimulus optimization (WP1)
2. Elucidate the behavioural relevance and attentional modulation of ICd neuronal activity (WP2)
3. Investigate the role of long-range projections on ICd neuronal activity (WP3)
In WP1, we developed custom written software in Matlab to control stimulus presentation [WP1.1] over a graphical user interface (GUI). Specifically, it can either present sounds systematically or randomly generate sounds with specific characteristics. It can also generate new sounds based on the feature of several input (“parent”) stimuli, which is required for the genetic optimization algorithm.
Using the OptiStimGUI, I was able to investigate the neuronal responses of the ICd in different areas. In general, the responses of these neurons are more pronounced in the awake animal in comparison to in anesthetized animals, which most previous publications had used. With the chronic calcium imaging technique, the responses of the same neurons before, during and after anesthesia were compared. The result of this work has been presented at the Annual Meeting of Society for Neuroscience and will be prepared for submitting for publication.
The next step was to establish a head-fixed two-alternative choice behavioral paradigm for mice. Similar to WP1, software and hardware have been developed under WP2 to control the behavioral experiments. Figure 3 shows a mouse performing the behavioral experiment in the setup, where it had to response by licking either the left or the right metal “lick port” depending on the sound it heard. Moreover, Optogenetics experiments have been successfully set up at the two photon microscope [WP3.1] where neurons in the inferior colliculus was activated by light, resulting in bursts of action potentials. The study of stimulation effects on animal behavior is being continued.

The development of stimulus optimization and operant conditioning paradigm has been utilized by the host department on related projects such as the study of tinnitus.
Presentation of results in conferences:
• Wong A.B. Geis H.R.-A.P. & Borst J.G.G. Chronic in vivo calcium imaging of the dorsal cortex of inferior colliculus in awake, behaving mice. Gordon Research Conference for Modulation of Neural Circuits and Behavior, Jun 2015, Hong Kong.
• Wong A.B. & Borst J.G.G. Chronic Ca2+ imaging reveals strong suppressive effects of anaesthesia on spontaneous and sound-evoked responses in dorsal inferior colliculus, The Dutch Neuroscience Meeting 2016, Jun 2016, Lunteren, the Netherlands; and the 46th Annual Meeting of the Society for Neuroscience, Nov 2016, San Diego, CA, USA
Public outreach:
The fellow has co-organized an open day event “Neem je brein waar” ( on 18th March, 2017 at the Departments of Neuroscience and of Psychiatry in Erasmus MC, in support of the Brain Awareness Week initiative from Dana foundation ( Over 200 visitors, ranging from children to elderlies, explored the laboratories and were introduced on the scientific research conducted at the departments through art, games, lectures and interactive workshops.
The Optimapic project opened up a multidisciplinary approach to studying auditory function at the inferior colliculus. The project demonstrated the feasibility of this approach, and the finding that neurons response very differently in awake animals showed us the importance of studying awake animals in physiology. This also demonstrates how surprisingly little we understand the auditory system in general, which is an essential step in figuring out the underlying mechanisms and potential treatment of audiological disorders such as tinnitus, noise trauma and age-related hearing loss.
Chronic calcium imaging in dorsal inferior colliculus