Memories of Fear
dag.stenberg at helsinki.fi
Mon Jan 3 06:46:16 EST 2000
Ron Blue wrote:
I looked up the article (Garcia et al., Nature 402:294-296, 1999).
I (too) wish to comment just shortly.
While it has been known for a long time that the amygdala is involved in
fear, the mechanisms of this involvement has mostly been unknown. The
anatomy and interconnections of the various nuclei of the amygdala have
been mapped in detail less than 10 years ago. It was shown in 1991 that
stimulation of the basolateral nucleus (BL) of the amygdala inhibits
neurons in the medial prefrontal nucleus. It has been shown, in the
'90s, that the auditory system projects to BL, and separately that both
unconditioned and conditioned stimuli induce long-term potentiation of
auditory-evoked events in the BL.
What these guys now showed (greatly shortened, hopefully not messed up
by me) was that neurons in the prelimbic (medial prefrontal, MPF) cortex
were inhibited by a fear stimulus, but less in response to a conditioned
stimulus, if the animals had been post-conditioned to reduce the
behavioral fear response (freezing). The degree of inhibition in MPF was
thus related to the level of CS-evoked freezing behavior. to find out
the involvement of the maygdala, they then made bi- or unilateral
amygdalectomy to some animals. Sham-lesioned animals had a stong
inhibition of MPF to fear-inducing CS, bilaterally lesioned no
inhibition, and unilaterally lesioned had suppressed inhibition of MPF
in the lesioned side. The freezing response correlated inversely with
the lesion: it was greatest in the sham-lesioned, intermediate in
unilaterally lesioned and less in the bilaterally lesioned.
The pathways (BL to MPF) remain to be determined, as the direct BL-MPF
pathway involves excitation.
The authors think that these experiments may illustrate the importance
of the MPF in decision-making: if the MPF predicts danger, its neurons
are strongly inhibited, and this is a signal to other circuits. The BL
projection to the MPF will teach the MPF whether there is danger or not.
My point with all this is that such experiments and their forthcoming
extensions tell us HOW various brain areas function on a
pathway-transmitter-cellularmessenger-genomic level, which is
enormously more useful for medical applications that just knowing THAT
these areas are in some way involved, or even just that their level of
excitation or inhibition (and pray - in what neurons of this complex
mass of circuits?) changes. In my view, the present work must be
followed by more detail work concerning cellular and molecular
mechanisms, and we will see such results in a few years.
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