Biomedical Engineering Reference
In-Depth Information
performances compared to spaced trials. Disruption of molecular processes by
pharmacological and genetic tools showed that memory formed by procedures
using spaced trials is dissectible into STM and subsequently three independent,
parallel phases: MTM, early long-term memory (eLTM), and late long-term mem-
ory (lLTM). MTM in the hours range requires constitutive PKC activity (Grünbaum
and Müller
1998
). Both eLTM and lLTM require PKA- and nitric oxide (NO)-
dependent processes for their formation (Müller
1996
,
2000
). However, eLTM,
retrievable 1-2 days after conditioning, requires translation whereas lLTM demands
for transcription (Friedrich et al.
2004
).
Recent experiments based on neuropharmacological manipulation or RNA inter-
ference of PER conditioning identifi ed several molecular processes important for
olfactory memory formation. Most importantly, these experiments demonstrate that
different molecular processes subtend different memory phases. For example, glu-
tamate and
N
-methyl- D-aspartate (NMDA) receptors are involved in MTM (Müßig
et al.
2010
) and eLTM formation but not in lLTM formation (Maleszka et al.
2000
;
Si et al.
2004
; Locatelli et al.
2005
; Müßig et al.
2010
). Alpha-bungarotoxin (BGT)-
sensitive nicotinic acetylcholine (nACh) receptors are involved in eLTM formation,
while BGT-insensitive nACh receptors are involved in memory retrieval (Gauthier
et al.
2006
). Intracellular calcium, adenylyl cyclase, cyclic nucleotide-gated chan-
nels, calmodulin (CaM), and CaMKII are all involved in lLTM formation but not in
eLTM formation (Perisse et al.
2009
; Matsumoto et al. unpublished data). A crucial
future challenge will be to clarify how these molecules interact for giving rise to the
different olfactory memory phases subtending retention.
The neuronal circuits processing the odor stimulus (CS) and the sucrose reward
(US) in PER conditioning are well described (Menzel
1999
; Giurfa
2007
; Giurfa
and Sandoz
2012
). The CS pathway includes the olfactory receptors located on the
antennae, the antennal lobes (ALs: primary olfactory centers), the mushroom bod-
ies (MBs: higher-order centers), and the lateral protocerebrum (premotor output
regions). Olfactory information detected at the level of the antennae is processed in
the ALs, which then send this information to the MBs input region (calyces) and to
the lateral protocerebrum via projection-neuron tracts. The MBs, with their intrin-
sic Kenyon cells, process input from different sensory modalities (Mobbs
1982
;
Abel et al.
2001
; Gronenberg
2001
) and their extrinsic neurons are multimodal
(Grünewald
1999
; Mauelshagen
1993
; Okada et al.
2007
; Haehnel and Menzel
2010
). Concerning the US pathway, information from sucrose receptors located on
the antennae and the proboscis is relayed to the subesophageal ganglion. Directly
or indirectly they contact the ventral unpaired median neuron number 1 of the
maxillary neuromere (VUMmx1 neuron), which projects widely in the ALs, the
calyces of the MBs, and the lateral protocerebrum. Activity of this individual neu-
ron can substitute for the US in classical conditioning assays (Hammer
1993
). The
ALs, the MBs, and the lateral protocerebrum are thus main convergence sites for
the CS and US pathways.
PER conditioning has allowed showing the existence of learning-dependent plas-
ticity in the CS and US pathways. Changes in neural activity and in synaptic archi-
tecture have been reported by application of electrophysiological, optophysiological,
and histological techniques (Hammer
1993
; Mauelshagen
1993
; Okada et al.
2007
;
