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TWiN 58: Tongue-Dragging Rescue Behavior in Mice

• 0:00 Introduction: Hosts Vincent Racaniello, Tim Cheung, and Vivian Morrison discuss a study on a newly observed "rescue-like" behavior in mice.

• 4:29 Study Overview: The study, published in Science Advances, shows that when a mouse encounters an unconscious "conspecific" (another mouse), it engages in behaviors, including tongue-dragging, that accelerate the unconscious mouse's recovery from anesthesia.

• 5:32 Tongue-Dragging Behavior: The behavior involves the "bystander" mouse sniffing, grooming, eye-licking, and, importantly, pulling on the tongue of the anesthetized mouse with its teeth.

• 6:57 Rodent Social Behavior: The hosts will talk about some of the neuromechanism involved.

• 12:57 Key Concepts: Three major themes: 1) circuit mapping in neuroscience, 2) triangulating hypotheses with multiple experimental approaches, and 3) smaller, well-tuned neural circuits can be more significant than larger, broadly activated ones.

• 15:33 Initial Observations: The bystander mice spend more time interacting with an anesthetized mouse than with a toy or a deceased mouse, indicating the behavior isn't mere curiosity.

• 17:29 Terminology: The players of this experiment include the "bystander" mouse which is the rescuer, and the unconscious "conspecific" mouse.

• 19:32 EMG Recordings: Electromyography (EMG) of jaw muscles differentiates sniffing, grooming, and tongue-dragging, with tongue-dragging showing the most muscle activation.

• 21:36 Sex Differences: Male mice engage in tongue-dragging regardless of familiarity with the anesthetized mouse, while females show a preference for familiar mice. Experiments proceed with males to avoid this variable.

• 23:28 Tongue Pinching: Pinching the tongue with forceps (without a bystander present) also accelerates recovery from anesthesia, indicating the tongue stimulation is key.

• 25:57 Anesthetized Mouse Circuit: The study traces the neural circuit in the anesthetized mouse, starting with the tongue.

• 28:09 Retrograde Tracing: Retrograde monosynaptic dyes and viruses are used to map the neural pathway from the tongue to the brainstem's mesencephalic trigeminal nucleus (MTN).

• 33:50 MTN to Locus Coeruleus: The MTN projects to the locus coeruleus (LC), a brainstem nucleus involved in arousal and norepinephrine release.

• 40:56 c-Fos Expression: Tongue-dragging leads to increased c-Fos expression (a marker of neuronal activation) in the LC of the anesthetized mouse.

• 41:51 Locus Coeruleus Activation: Direct recordings show increased LC activity after tongue pinching, more so than after hind paw or back skin pinching.

• 48:14 Chemogenetics (DREADDs): Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are used to inhibit or activate MTN neurons, affecting recovery time from anesthesia.

• 53:24 Bystander Mouse Circuit: The study investigates the neural circuit in the bystander mouse, starting with a c-Fos screen.

• 55:55 Brain Regions Involved: The paraventricular nucleus of the thalamus (PVT) and the shell of the nucleus accumbens (NAc) show high c-Fos levels during tongue-dragging.

• 58:35 Calcium Imaging: Genetically encoded calcium sensors show increased calcium activity (indicating neuronal activation) in the PVT during sniffing, grooming, and tongue-dragging.

• 1:00:34 Modulation of Behavior: Inhibiting or activating the PVT using DREADDs reduces or increases tongue-dragging behavior, respectively.

• 1:03:15 Nucleus Accumbens Single cell-level Activity: Fewer NAc neurons are activated, yet calcium peak levels are high, during tongue dragging behavior in bystander mice.

• 1:05:50 Parvalbumin Interneurons: These inhibitory interneurons in the NAc are hypothesized to be crucial for tongue-dragging, inhibiting other NAc neurons.

• 1:07:31 Interneuron Manipulation: Inhibiting or activating these parvalbumin interneurons using DREADDs affects the timing and frequency of tongue-dragging and sniffing.

• 1:08:30 Downstream Target: The downstream target of these NAc interneurons is identified as dopamine receptor 1 (D1)-expressing medium spiny neurons.

• 1:08:52 Discussion of Mechanism: The presenters discuss the complex interactions and potential roles of vision and smell in the behavior, and speculate about real-life implications.

• 1:11:59 Discussion in Wild Mice: The presenters discuss if tongue-dragging behaviour might happen in wild mice to potentially unblock airways.