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Morkeliph
02-02-2006, 8:55 PM
Hey, seeing as you're a molecular biologist and all, maybe you can answer this for me. I was talking with my professor the other day about the physiological mechanisms of classical conditioning in animals and humans. I'm not sure how much you deal with respondent conditioning so perhaps first I should explain what I mean by this; hopefully this wont be too lengthy or technical.

I'm going to presume that you already understand the general principle of classical conditioning, US, UR, CS, CR and the like. Extinction, of course, occurs when the CS is presented repeatedly without the US and eventually fails to produce a CR. Spontaneous recovery, as you might know, is when after a period of rest from extinction, the CS is again presented alone and elicits a CR of some magnitude greater than when extinction ended. Additionally, you may remember that second, third and subsequent acquisition trainings occur more rapidly than the first or prior training. Disinhibition occurs when after a CR is extinguished, the CS is presented along with some salient, novel stimulus and the CR is again elicited.

Why am I rehearsing these things to you? Well, it's fairly obvious that extinction training does not "erase" prior aquisition training because the organism is never quite the same afterwards. Spontaneous recovery, disinhibition and rapid reacquisition all show that in some way, the organism is still different from how it was prior to initial conditioning. The general theory behind this is as follows: extinction training is not a "breaking of the US-CS association" but actually the conditioning of a second, inhibitory response. This response is more fragile and more easily disrupted than excitatory responses. It disrupts with time (spontaneous recovery) and deviations from training conditions (disinhibition). In other words, it's similar to a kind of conditioned suppression.

EDIT (FINISHING THE POST): Presumably, if we knew more about the physiology of classical conditioning, as in what physically is going on inside the organism as they learn new conditioned responses, then we might better understand why these events occur. Many studies have shown that when organisms learn new behaviors or responses, nerve growth occurs that actually creates new neural connections. In other words, neurons are making new connections to each other that enable the organism to learn as the result of experience. Other studies show that "forgetting" may be partially the result of deterioration between neural connections, often due to disuse. So one reason why you cannot remember math as well if you haven't done it in a while is because your neurons have deteriorated that faciliated mathematical behavior. However, neurons grow more readily than they deteriorate, and deterioration may not be the only way we "forget" things.

What I suggest, and I doubt it is highly original, is that in classical conditioning and perhaps other forms of learning, when a new response is acquired in acquisition, new neural connections are made that don't deteriorate with mere extinction training. Instead, what actually happens in extinction is that you learn an inhibitory response that prevents those nerves from firing. This second response might be just some form of chemical blocking that stops neurons from responsing (perhaps I'll make a diagram). This "chemical inhibitor" is less permanent that the physical neural connections that occur in acquisition training and thus deteriorates faster. In other words, spontaneous recovery can be understood as a weaking on the strength of the chemical inhibition with the mere passage of time. Since the neurons are already connected, the mechanisms for a conditioned response are already in place and the only thing preventing its occurrence is the "chemical block." So obviously, when this chemical block weakens over time, then it can be expected that it will be less able to prevent a response from occurring, and some response may be observed.

Secondly, because the etablishment of a chemical blocking is a conditioned response in and of itself, variance from training conditions (the environmental conditions during extinction training) will result in a lessened ability to elicit the inhibitory response. This is the same principle as respondent generalization: as the characteristics of a stimulus increasing depart from those present in acquisition training, the magnitude of the response increasingly diminishes. This would seem to account for disinhibition. When a novel stimulus is presented that wasn't present in extinction training, this is a variation from the conditions in which inhibition was acquired, and thus a weaker inhibitory response in elicited, resulting in lessened ability to prevent the excitatory response.

Finally, because the neural connections are already in place and the only thing preventing their functioning is a conditioned inhibitory response, it makes sense why reaquisition occurs more rapidly with subsequent trainings. The "hardware" is already installed; it doesn't have to be built in the second time. All that has to happen is a weakening of the inhibitory response and the suppressed excitatory response will reappear. All of these seem like potential evidence for the inhibitory response theory and imply that learning occurs because of neural growth.

This is where you (finally) come in. I was thinking about it the other day, and classical conditioning has been demonstrated in unicellular microorganisms. In these organisms, obviously, there are no neurons to make connections to one another that facilitate respondent learning. This being the case, what actually happens physically within the microorganism that enables it to learn a conditioned response? I figured I'd ask you because you probably know a lot more about the physiology of unicellular organisms than most people, and you might be able to explain to me how they learn. Depending on the actual mechanisms, they may or may not be expected to show spontaneous recovery, disinhibition and rapid reaquisition. If they do, then there are serious research possibilites involving the mechanisms of inhibitory response theory. If they don't, then inhibitory responses obviously have something to do with the physiology of nerve cells and neural activity. I don't even know if protozoa have been studied for extinction or not. Perhaps respondent learning is permanent in these organisms, but I doubt it (I think they habituate according to research). Anyway, I was wondering if you could share with me your knowledge of microbiology in hopes of helping me understand the mechanics of learning processes.

Morkeliph
02-06-2006, 3:13 PM
Thanks Neo for defending this thread. I'm sorry it took me so long to finish it...the super bowl and all prevented me from returning immediately to fix it. Anyway, anyone who wants to participate is welcome now that the initial discussion is established. Thanks again.

GenocideAlive
02-06-2006, 3:53 PM
I'm not sure how familiar you are with biology, but you're referring to a negative control acting on nerves which I'm fairly sure would just be a positive control. Any body going out of its way to make a chemical to inhibit nerves would be wasting its resources. It'd be far better served to simply stop making those chemical transmitters of the nerve. When you "reawaken" the nerve through whatever stimulus, you're probably just going through the process of repopulating those nerves with their appropriate chemicals (and perhaps maintenance or mild restructuring) so that the nerves can fire once again.

In short, if you're paying some dude to walk across a street at 3PM every day, you wouldn't hire some lady to run out there and stop him from walking across the street every day at 3PM. You'd just tell him to take a hike.

In regard to the unicellular organisms being conditioned to response, I'd first be curious to know which organism we're talking about and to what they're responding. Protozoa is a rather broad category encompassing multiple types of protozoans with various methods of motility. I could give multiple responses to what you've written with all sorts of details, but you'd probably get bored and annoyed because it'd be more like a lecture on general microbiology. Give me a little bit of an example of CS/CR please, or at least a direction you want me to take this.

Morkeliph
02-06-2006, 4:34 PM
Interesting point with regards to positive and negative control. I'm obviously not vary familiar with these concepts, but I'll try to look more into them and see where my hypothesis needs adapting.

As for the conditioning demonstrated in protozoa, I'm not sure what exact species and or methods were used, but maybe I can find an article. From what I remember it went a little like this:

The microorganism (a paramecium perhaps?) was under microscope on its slide. The experimenter presented a neutral stimulus (changing light conditions perhaps, or something arbitrary like that) and shortly afterward dropped a small weight on the slide (US), eliciting a startle response (UR) of contraction or something of that nature. This pairing occured repeatedly until finally just the light (CS) elicited a similar startle response (CR) in the organism. A similar study has also been done demonstrating habituation where the US (dropped weight) was presented repeatedly and a the UR (startle response) gradually diminished and "disappeared."

I don't know if that helps much, but it illustrates at least one way in which the microorganism may be conditioned. What I'm really asking is what you know about the physiological processes (in general) that occur within microorganisms that trigger certain behavior. I'm assuming it has something to do with changes in the chemistry of the cytoplasm and the activation of enzymes, organelles, etc., but I'm not sure how this might fit into a conditioned inhibitory response model.

If you're familiar with Rescorla's study on S-S pairing, I can explain a little bit more about how the inhibitory response might actually occur. Basically, his study showed that in whatever happens to cause respondent conditioning, the part of the organism that responds to the CS learns to communicate with that of the US, in stead of directly to that of the UR. In other words, the neurons that engage when the dog hears the bell make connections to the nerves that engage when food is in the mouth rather than connecting to those that activate salivation. All that it would require then to inhibit conditioned responding is a disruption of the CS-US neural connection at some point. Maybe this is just learning to not fire a neuron, but whatever it is, it must be susceptible to weakening with time and it would seem that this action (or inaction) is a conditioned response in itself. To me it seems like it should be something active rather than inactive because of disinhibition and rapid reaquisition, but maybe that's just because of how I'm used to looking at it.

GenocideAlive
02-08-2006, 11:35 AM
Interesting point with regards to positive and negative control. I'm obviously not vary familiar with these concepts, but I'll try to look more into them and see where my hypothesis needs adapting.
Negative controls are typically applied where you are trying to regulate a necessary or ongoing activity. Like stoplights for traffic--you can regulate its speed or activity when it's getting to be problematic. Positive controls are put into place for activities that aren't always needed. Sort of like supplying gas for traffic in small towns--you can simply give people gas if they need to get some quick work done, and stop supplying it when they've succeeded.

The basic example in biology is the role of inhibitory proteins in transcription. If you are presented with a special need, you can bind a few regulatory factors to up-regulate production of a needed special protein (PC). If you are simply producing basic enzymes for food breakdown and you have digested the food and don't need any more, you bind down-regulating factors to temporarily stop production (NC).
I don't know if that helps much, but it illustrates at least one way in which the microorganism may be conditioned. What I'm really asking is what you know about the physiological processes (in general) that occur within microorganisms that trigger certain behavior. I'm assuming it has something to do with changes in the chemistry of the cytoplasm and the activation of enzymes, organelles, etc., but I'm not sure how this might fit into a conditioned inhibitory response model.
Ugh. I don't know how complicated this is or isn't going to get, but let's see if I can keep it comprehensible.

Typically single-cell organisms work on the basis of "receptor saturation". There are a determined number of receptors on the cell that function to perform a specific task (like detecting light, etc.) and become "bound" when they recieve their target molecule. In this case, you probably have a light-activated membrane receptor protein that releases a particular chemical "L" when exposed to a particular strength of light. Basically the conformation of the protein changes when it receives enough light-energy to overcome steric hindrances.

The cell can sometimes determine the amount of light by the ubiquitousness of the "L" chemical inside of the cell. Sometimes it's an all-or-nothing response, like a nerve, in which there is a "threshold" or a specific saturation of the chemical that will behave as an "on" or "off" setting. Basically it works out that the "L" chemical floating around in the cytoplasm binds to yet other molecules that form a complex that will then bind to the receptors of the "contraction" mediator.

I don't claim to know the specifics of this cell's functions without knowing the specifics of the cell itself, but if this paramecium's cell function is damaged or hindered by the shaking of the slide then it's simply connecting simple functions to prevent damage. Its contraction is an evolved function to apparently cope with this damage or hindrance (shaking). If it is concerned about water-loss or damaging proteins embedded in its membrane (which can also occur during prolonged intense lighting), then there's a possibility that it can begin to release the factors responsible for contraction with a much lower binding efficiency. Simply that ANY of chemical "L" has bound begins to signal to the cell that it needs to contract. And, eventually, it reverts back to its old chemistry.

Basically I think this study changes the amount of chemical "L" needed to activate the paramecium's response, but otherwise I don't think it's taking two unrelated behaviors and connecting them. If that makes sense.

This is a blanket assumption and there are a lot of factors in there that I would like to have fleshed out so that I can determine a more definite answer. Hope this helps?

Morkeliph
02-08-2006, 5:48 PM
Yeah, that was basically what I was looking for. I just figured that unicellular organisms most regulate activity via chemical production within the cytoplasm. In the case of conditioning a microorganism, one must be somehow eliciting a type of chemical production in response to a conditioned stimulus. Rather interesting really. I wonder then if individual human cells can be classically conditioned to do certain things with the presentation of seemingly arbitrary stimuli. There might be interesting research to be done on cancer in that direction, amongst other things.

Thanks GenocideAlive, that helps me with what I was basically looking for. I'll let you know if I have any new questions or information.