Wednesday, July 21, 2004

Thinking Outside the Box

One of the thinks that makes schools of higher learning fun is when you learn that your much-despised ninth-grade teacher was dead wrong about something.  Not that I recommend going to medical school for that reason.  Too much work, not enough sleep.  But, you take your jollies where you can get them.

For those of you who have not had the pleasure of walking around for six months smelling like formaldehyde -- a rite of passage courtesy of gross anatomy -- I provide a glimpse of one of the other sources of pleasure in higher learning: thinking outside the box.  In primary and secondary education, science is taught as a series of facts.  You memorize the facts, you get a good grade.  Yes, from time to time there is lip service for the goal of teaching students how to think, instead of what to think; but this is falling by the wayside, as the effect of enforced mediocrity (aka No Child Left Behind) is felt -- increasingly -- across our great land.  If students don't get good scores on standardized tests, the school could loose funding.  This, predictably, will lead to a bunch of students who all think alike:   the Emperor's New Clones. 

Rant tangents aside, reveling in the belief that blogging might be able to make up for the deficiencies in our educational system, let's take a look at some of those things that you might have been taught about biology, that are turning out to be wrong. 

The Cerebellum Coordinates Muscle Movements.  This is taught in high school biology.  It is accepted as fact.  It will be on the test.  But it is only partly true. 

Copyright © 2004 Cell Press.
Neuron, Vol 42, 973-982, 24 June 2004

Long-Term Synaptic Changes Induced in the Cerebellar Cortex by Fear Conditioning
Benedetto Sacchetti 1, Bibiana Scelfo 1, Filippo Tempia 2, and Piergiorgio Strata 1,3

1Rita Levi-Montalcini Center for Brain Repair, Department of Neuroscience, University of Turin, Corso Raffaello 30, I-10125 Turin, Italy
2Department of Internal Medicine, Section of Human Physiology, University of Perugia, Via del Giochetto, I-06126 Perugia, Italy
3Rehabilitation Hospital and Research Institute, Santa Lucia Foundation, Via Ardeatina 306, I-00179 Rome, Italy

To better understand learning mechanisms, one needs to study synaptic plasticity induced by behavioral training. Recently, it has been demonstrated that the cerebellum is involved in the consolidation of fear memory. Nevertheless, how the cerebellum contributes to emotional behavior is far from known. In cerebellar slices at 10 min and 24 hr following fear conditioning, we found a long-lasting potentiation of the synapse between parallel fibers and Purkinje cells in vermal lobules V-VI, but not in the climbing fiber synapses. The mechanism is postsynaptic, due to an increased AMPA response. In addition, in hotfoot mice with a primary deficiency of the parallel fiber to Purkinje cell synapse, cued (but not contextual) fear conditioning is affected. We propose that this synapse plays an important role in the learned fear and that its long-term potentiation may represent a contribution to the neural substrate of fear memory.

You need a subscription for the entire text, but I will give you the bottom line.  My personal theory is that nothing in the body serves only one function.  Ok, maybe the earlobe has only one function.  Everything else has at least two functions.  Dr. Sachetti et. al.  have demonstrated that the cerebellum is involved in fear conditioning, something previously thought to be seated in the amygdala.  Naturally, their work is really an extension of work does previously by others:

[...] A growing body of data suggests that the cerebellum is involved in fear behavior both in experimental animals and humans (Snider and Maiti, 1976; Heath et al., 1981; Supple et al., 1987, 1988; Supple and Leaton, 1990; Sebastiani et al., 1992; Supple and Kapp, 1993; Schmahmann and Sherman, 1998; Parvizi et al., 2001; Maschke et al., 2002; Sacchetti et al., 2002b). Stimulation of cerebellar vermis induces a complex behavioral pattern indicative of emotional arousal in animals (Snider and Maiti, 1976) and elicits psychotic symptoms in humans (Heath et al., 1981). Cerebellar pathologies have also been correlated with various emotional disorders such as depression and autism (Snider and Maiti, 1976; Heath et al., 1981; Schmahmann and Sherman, 1998; Parvizi et al., 2001). In addition, cerebellar dysfunction affects autonomic and behavioral conditioned fear responses (Supple et al., 1987, 1988; Supple and Leaton, 1990; Sebastiani et al., 1992; Supple and Kapp, 1993; Schmahmann and Sherman, 1998; Maschke et al., 2002; Sacchetti et al., 2002b). Nevertheless, how the cerebellum contributes to emotional spontaneous and learned behavior is not known. A recent report showed that the reversible inactivation of the cerebellar cortex abolishes the retention of fear conditioning (Sacchetti et al., 2002b). This effect was obtained by injecting tetrodotoxin after the acquisition session and performing the retention session when the tetrodotoxin reversible blockade was over.

[...] While for the vestibulo-ocular reflex and the eye blink conditioning there is a satisfactory model of operation, nothing is known about fear conditioning. Therefore, the aim of the present work is to identify possible long-term synaptic plasticity in the cerebellar cortex associated with emotional memory. [...]

Skip down to the conclusion:

[...] In this paper, we show that following fear conditioning, obtained by associating a sound with an electric shock, there is a long-term change in the PF-PC synapses and that a cerebellar dysfunction due to a primary impairment of these synapses does not prevent the acquisition, but impairs short- and long-term retention, of this learning paradigm.

[...] In the hotfoot  mice, we found no statistically significant difference in the spontaneous anxiety-related behavior. Therefore, the amnesic effects observed in these mice are likely not due to the interference with anxiety state. In addition, our data show that the cerebellum does not simply control the motor responses related to emotions. In fact, in the hotfoot mice, the freezing response is still present in the acquisition phase and in the context retention, but it is selectively abolished in the cued retention. Therefore, our experiments suggest that the cerebellum is a link between sensory stimulus (a sound), its emotional significance, and the correct motor behavior. This view is supported by our demonstration that in normal animals, persistent modifications of the PF-PC synapses occur in those cerebellar lobuli where there is a convergence of acoustic and nociceptive stimuli.

Therefore, the PF-PC synapses in the cerebellum do more that just coordinate the various movements involved in the fear response.  They are involved in the association between the emotional state and the conditioned behaviors.  Unfortunately, our school are turning out kids for whom learning is nothing more than a series of conditioned responses: see the word "cerebellum", check the box "balance and coordination."

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