Are YOU a Molecular Biologist?
Or do you KNOW any molecular biologists?
I have good news about my 12 April 2021 piece with Dr. Gallistel. The piece really took off, has >35,000 views now, and even got Dr. Gallistel some help in his quest to find what he wants to find.
Below is Dr. Gallistel’s basic pitch to molecular biologists.
If you’re a molecular biologist, then please look at the proposal below and get in touch with Dr. Gallistel if you’re interested—or if you have any questions/ideas/criticisms.
And if you know any molecular biologists, then please send them a link to this piece that you’re reading right now so that they can take a look.
Here’s Dr. Gallistel’s basic pitch about what he wants to do:
Ariadne’s Thread
There is a glutaminergic synapse between the parallel fiber and the Purkinje-cell.
Inside this synapse is a mGluR7 metabotropic receptor.
This receptor leads into the labyrinth that ultimately contains the engram.
This receptor is at the start of an intracellular biochemical cascade.
The cascade terminates at the pause-producing inward-rectifying K+ channel.
Somewhere in that cascade is the engram.
The thread leads to the engram.
The thread also leads onward to a mechanism that translates the engram into a timed shutdown (of the mechanism that generates the spontaneous firing).
The thread can be followed from both ends (like a chromosome-walk).
Recognizing the Engram
Before the engram, the information about the CS–US interval will NOT be seen in the biochemical stages’ durations/latencies.
But after the engram, it WILL be.
You need to attack from both ends!
There must be a one-to-one mapping between CS–US intervals and (some aspect of) engram-structure.
We know this because the CS-pauses’ mean-duration/standard-deviation each are a scalar function of the previously-experienced CS–US intervals. (Monotonic functions are invertible.)
And there must also be a one-to-one mapping between (some aspect of) engram-structure and the potassium-channel opening’s duration (that generates the long ISI that encodes the CS–US interval).
Here’s the background:
The standard theory of memory in neuroscience—synaptic plasticity—does not attempt to explain the most obvious fact about memory: that it is a repository of learned facts about the experienced world. The engram, the material basis of memory, must have a structure like that of the polynucleotides, a structure that transparently enables the encoding of facts. Moreover, the fact-encoding structures must be rapidly generable at low energetic cost in the course of a brain’s computations, which rules out computation in recursive neural networks. These elementary considerations imply that the facts of experience are encoded at the level of individual molecular structures. The simplest and most common facts of experience are the quantitative facts, such as the durations of intervals. These are also the most readily manipulable facts in experimental preparations.
This is the opportunity:
Research by Fredrik Johansson in the laboratory of Germund Hesslow in the Medical School of Lund University has revealed the molecular starting point and the molecular endpoint of an intracellular biochemical cascade that accesses a molecular encoding of the duration of a learned inter-event interval. This engram mediates the timing of the conditioned blink of the eye. These findings offer molecular biologists the opportunity to follow a systematic research strategy to locate the molecular structure that encodes a learned and remembered inter-event interval. They can move along the cascade from both ends, somewhat like an old-fashioned chromosome walk. So long as they are looking at a pre-engram step, the information about the duration of the interval will not be seen in the biochemistry. So long as they are on the other side, the output side, it will be seen in the biochemistry. Once the engram stage has been located, one can determine what the structural change at that state is that encodes the interval.
This is the payoff:
The discovery of the engram will produce a revolution in neuroscience as profound and far-reaching as the revolution in biology produced by the discovery of the molecular structure of the gene, because the engram is the foundation of a brain’s ability to compute.
Here are some relevant references:
“Memory trace and timing mechanism localized to cerebellar Purkinje cells”