Podcast Summary: This Week in Neuroscience, Episode 53

"Slowing time by cooling the brain"
Date: July 29, 2024
Host: Vincent Racaniello
Guests: Joseph Paton & Philippe Rodriguez (Champalimaud Foundation, Lisbon)
Panelists: Jason Shepherd, Tim Chung, Vivian Morrison

Episode Overview

This episode delves into recent research exploring how precise cooling of specific brain regions can alter the perception of time, using behavioral tasks in rodents as a model. The conversation centers on a Nature Neuroscience paper by the Paton lab, highlighting how manipulating temperature in the striatum causally slows or speeds up an animal's internal clock for making time-based decisions. The episode discusses the science of temporal processing in the brain, the experimental design, and the broader implications for neuroscience and neuropsychiatric conditions.

Key Discussion Points & Insights

1. Introduction to Guests and Their Backgrounds

• Joseph Paton (PI) and Philippe Rodriguez (recently completed PhD, now postdoc) join from the Champalimaud Foundation in Lisbon.
  • Paton, originally from the US, has worked in Lisbon for 16 years, drawn by the institute's unique atmosphere and resources ([02:15]).
  • The Center’s name, "Champalimaud Center for the Unknown," reflects Portugal’s history of exploration ([03:21]).
  • PhD program described as a hybrid American-European model with coursework and rotations ([05:20], [06:20]).

2. Temporal Processing in the Brain: Why It Matters

• Time is fundamental to organizing behavior; animals must recognize not only the order of events but the intervals between them ([07:56]–[14:24]).
  • Philippe Rodriguez explains:

    "Behavior unfolds through time... systems that evolve to control that behavior have to have dealt with time in one form or the other..." ([07:59])

  • Tim Chung and others clarify the difference between circadian (24-hour) timing versus "interval timing" (seconds to minutes), which is more flexible and relevant to adaptive behaviors ([08:43]–[10:45]).

Naturalistic Task Analogies

• Interval timing tasks in the lab (e.g., rats learning to press levers based on how long a light is on) are analogous to foraging in the wild ([11:22]–[12:40]).

3. Neuronal Basis of Timing: Is There a Brain Clock?

• The panel debates whether time is tracked by explicit neural "clocks" or is an emergent property of population dynamics.
  • Philippe Rodriguez:

    “Duration or the time between events is... distributed in the dynamics of populations of neurons.” ([17:29])

  • Uses the analogy of ripples in a pond: “...some stimulus triggers a sequence...from which you can decode how much time has passed...” ([17:29])
  • Joseph Paton and others point out multiple forms of timing in the brain—circadian versus interval, and the importance of population dynamics rather than a single central clock ([19:07]–[22:13]).

4. Experimental Approach: Manipulating Brain Temperature to Alter Timing

Rationale and Methods

• Previous work showed faster striatal dynamics correlated with reporting "long" intervals; slower dynamics with "short" ([22:32]).
• Needed a causal test: Could manipulating the speed (but not the pattern) of neural activity change subjective timing?
• Cooling or warming the striatum using a precisely controlled Peltier device allowed bidirectional manipulation ([29:07]–[29:46]).
  • Device development described as iterative and collaborative, with practical challenges ([29:07]).
  • Inspired by similar studies in songbirds (Mike Long’s work), but applied graded manipulations rather than full cooling to inactivate ([31:08]).

Channelrhodopsin Experiment

• To observe dynamics in anesthetized animals, channelrhodopsin was used to trigger reliable, repeatable brain responses, akin to “throwing a stone in the water to see the ripple” ([32:27]–[34:20], [35:48]).

5. Main Findings

a. Temperature Directly Alters Internal Timing

• Behavioral Experiment: Rats perform an interval categorization task—judging if the time between two beeps is shorter or longer than 1.5 seconds ([38:32]).

  • Cooling the striatum: Rats more likely to report "short" for ambiguous intervals.
  • Heating: More likely to report "long."
  • The effect is most pronounced for ambiguous intervals near the decision boundary ([43:34], [46:05]).

  Key Quote:

  • Paton:

    “If you just... had the same effect on all stimuli, right, that would be maybe consistent with just inducing some kind of motor bias. The fact that you’re getting this consistent bias specifically for those stimuli that are closer to the decision boundary... is consistent with actually having changed the latent representation...” ([47:11])

b. Effects Not Fully Attributed to Movement

• Two behavioral conditions tested: one where the animal was free to move; another where it was required to keep its snout in place ([48:11]–[51:41]).
  • Movement constraints didn't eliminate the timing effect, suggesting the manipulation acted on internal time representation, not just motor behavior.

c. Subtler Effects on Movement Vigor

• Temperature changes produced a non-monotonic effect on movement speed: deviations from normal (both hotter and colder) slowed response speed, independent of their impact on discrete timing judgments ([54:13]–[57:36]).
  • This is linked to baseline striatal activity; lower activity correlated with longer reaction times ([58:23]).
  • Analogous to Parkinson’s bradykinesia, where striatal circuits control movement vigor.

d. Adaptation to Chronically Altered Timing

• With repeated temperature manipulation over sessions, animals adapted—the timing effect diminished ([60:38]).

  • The team designed a control where task boundaries shifted, and animals learned to track these changes, mirroring their adaptation to temperature changes.

  Paton:

  “If I gave you a stopwatch... and I changed the speed of the stopwatch... But if I keep telling you you're getting them wrong, then you're just going to adjust your decision making to the new speed of the clock.” ([63:36])

6. Theoretical and Clinical Implications

• The research offers a causal demonstration that altering the speed of striatal population dynamics shifts in how animals judge elapsed time.
• Clinical tie-ins with dopaminergic system dysfunction: ADHD, Parkinson’s, etc.
  • Vivian Morrison: “That was one of the things that this paper made me think of... my own experience of time blindness and time elasticity...” ([40:48])
  • Paton: “Lots of different disorders that are thought to involve the dopaminergic system also affect various aspects of timing behaviors...” ([41:36])
• Brief mention of Feynman’s anecdote on body temperature and time perception, with clarification that humans regulate brain temperature tightly, but fevers can temporarily alter temporal judgment ([67:13]–[67:45]).

Notable Quotes & Memorable Moments

• Paton: “We try and let the science guide the timeline... so students don't fossilize here.” ([06:20])
• Chung, on the interval timing task:
  “What was mind blowing to me... was that the rat... can learn some of the behavior like that...” ([14:24])
• Rodriguez:
  “The main part of that summary is that we could actually use temperature for the, for what we wanted to do then in the behavioral experiments, because it really seemed like temperature was slowing down dynamics...” ([36:39])
• Morrison:
  “That was one of the things that this paper made me think of as I was reflecting on my own experience of time blindness and time elasticity and just consistently misjudging how much time has passed...” ([40:48])

Important Timestamps

| Timestamp | Segment / Highlight | |------------|----------------------------------------------------------------------------------------------------------| | 02:15 | Paton describes moving to Lisbon and the institute’s unique mission | | 07:56 | Introduction to the significance of time in behavior | | 17:29 | Analogy of neural timing as ripples in a pond | | 22:32 | Setting up the causal experimental question: manipulating speed of dynamics | | 29:07 | Description of the temperature manipulation device and engineering challenges | | 32:27 | Channelrhodopsin experiment for controlled “ripples” in neural activity | | 38:32 | Description of the behavioral interval timing task in rats | | 43:34 | Results: cooling causes “short” bias, heating “long” bias, especially for ambiguous intervals | | 54:13 | Effects of temperature on movement kinematics: non-monotonic changes in speed | | 60:38 | Adaptation to chronic changes: behavior normalizes as animals learn over multiple sessions | | 67:13 | Discussion of Feynman’s anecdote and body temperature–time perception in humans |

Flow and Tone

The episode was lively, friendly, and intellectually rigorous, with easy camaraderie among panelists and guests. The scientists responded thoughtfully to technical and conceptual questions, provided relatable analogies (e.g., ripples in a pond, stopwatch running fast/slow), and welcomed both scientific and personal reflections.

Conclusion

This episode provided a rich, accessible exploration of how manipulating brain temperature reveals the role of neural dynamics in interval timing. The findings support the idea that the brain’s sense of timing is embedded in the speed of population dynamics, not a centralized clock, offering new insight into temporal cognition and its disorders. The panel discussed the experimental challenges, implications for understanding movement and motivation, and the adaptability of neural circuits faced with enduring changes. Listeners were left with an appreciation for the ingenuity of experimental neuroscience and the fundamental role of time in brain function.