Dieter Jaeger: Multiscale assessment of fast cortical dynamics with widefield and 2P imaging in mice in a lick decision making task

Abstract

To understand cortical processing, activity needs to be assessed at subcellular, cellular, and network levels during behavior.  We have used a left/right lick decision making task with a delay across our laboratories to study motor planning and execution at the levels of synaptic transmission, dendritic integration, and network interactions.  On the subcellular/cellular level our hypothesis is that input to layer 1 in anterolateral motor cortex (ALM) from the ventromedial motor thalamus (VM) engages both local NGNF interneurons and direct dendritic excitation input to control superlinear dendritic responses that can be imaged as calcium events. We performed continuous 2-plane Ca2+ imaging of layer 5 pyramidal tract (PT) cell dendritic tufts and trunks of ALM over days. We found that a proportion of dendrites encoded for task relevant variables such as choice or trial epoch. In general, we found that PT cells encode even within cells for multiple different task related aspects, most prominently during the post-stimulus delay and during lick movement preparation and execution.

To analyze L1 input to PT cells, we imaged glutamate activity. We found a surprisingly, steep increase in glutamate release during stimulus presentation which was not found while Ca2+ imaging PT dendrites, indicating a non-linear synaptic transfer function. To understand fast signal processing at the network level, we employed the JEDI-1P voltage sensor with soma-targeted expression in excitatory neurons to perform wide-field imaging.  Imaging was performed through a cleared intact skull in adult head-fixed mice at a frame rate of 200 Hz.

We find that the contralateral sensory and motor cortical areas show clear lick related activity.  Using Independent Component Analysis (ICA), a number of different task-related functional networks with distinct voltage dynamics could be identified. These networks each follow a distinct temporal dynamic during the task and reveal multiplexed task responses in different cortical networks related to sensory processing, motor preparation, and motor execution. Additionally, a coherence analysis in different frequencies showed that these networks in some cases are coupled through oscillatory activity. Overall, our findings indicate that neural activity at both single dendrite and network levels multiplexes different aspects of task processing.

Duration of the talk:

Approx. 50 minutes, then general and specialized discussion.

Where:

IMBIT, Nexus Lab, George-Köhler-Allee 201, 79110 Freiburg im Breisgau

More about the speaker and his research

Dieter Jaeger

Host

Ilka Diester