amnesiac: Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

Gene name - amnesiac

Synonyms -

Cytological map position - 19A1

Function - "memory" neuropeptide

Keywords - neural, brain, memory, hormones

Symbol - amn

FlyBase ID: FBgn0086782

Genetic map position - 1-[64]

Classification - secreted neuropeptide

Cellular location - secreted

NCBI links: Precomputed BLAST | Entrez Gene

Memory in both vertebrates and invertebrates involves increasing the efficiency of the synaptic function, otherwise known as long term potentiation. Efficiency is increased as a result of synaptic changes wrought by repeated firing of the synapse. What are the biological meditors of this synaptic change? dunce and rutabaga are involved in what has become known as the memory pathway, also known biochemically as the adenylate cyclase second messenger pathway, which is activated by synaptic activity.

What are the biological activators of the memory pathway? One way to find genes that are functionally related in a linear pathway is to isolate the suppressors of these genes. amnesiac was isolated as a suppressor of dunce mutant phenotype (Quinn, 1979). Behavioral tests indicate that amnesiac mutants are defective in tests of associative learning (Tully, 1990). Evolutionary homologies of Amnesiac provide clues as to its function. PACAP (pituitary adenylate cyclase-activating polypeptide) and GHRH (growth hormone releasing hormone) are vertebrate peptides able to activate the adenylate cyclase pathway, acting through G-protein coupled receptors. Two potential peptides of Amnesiac are homologous to PACAP and GHRH (Feany, 1995). Thus Amnesiac is a peptide that has the potential to be secreted by neurons in the memory pathway, thereby activating the adenyl cyclase second messenger pathway.

PACAP-like activity has been detected in larvae and neuromuscular junctions that function in the adenylyl cyclase second messenger system. The vertebrate PACAP38 triggers two muscular responses in Drosophila: an immediate depolarization and a late enhancement (Zhong, 1995b). Antibody to vertebrate PACAP-38 stains segmentally repeated larval CNS neurons as well as motor nerve terminals (Zhong, 1996). It has long been thought that the neuromuscular synapse may be a good model for the synaptic basis of learning. Amnesiac and the PACAP-like activity demonstrated by Zhong could be functioning through a similar mechanism. Binding of a PACAP-like peptide to its receptors leads to activation of Rutabaga-adenylyl cyclase by the Galpha subunit and of Ras1/Raf by the Gbeta-gamma complex: the pathways then converge to modulate potassium ion-channel activity (Zhong, 1995a and Zhong, 1996).

Memory survives metamorphosis. Larvae taught to avoid an odor retain the ability to avoid the odor as adults, 8 days later. Training of amnesiac mutant larvae failed to establish any detectable learning in larvae or memory retention as adults (Tully, 1994).

Ethanol intoxication in Drosophila: genetic and pharmacological evidence for regulation by the cAMP signaling pathway

Upon exposure to ethanol, adult Drosophila display behaviors that are similar to acute ethanol intoxication in rodents and humans. Within minutes of exposure to ethanol vapor, flies first become hyperactive and disoriented and then uncoordinated and sedated. After approximately 20 min of exposure they become immobile, but nevertheless recover 5-10 min after ethanol is withdrawn. cheapdate, a mutant with enhanced sensitivity to ethanol, has been identified as a contributory factor, using an inebriometer to measure ethanol-induced loss of postural control. An inebriometer is a device that allows a quantitative assessment of ethanol-induced loss of postural control. The inebriometer is an approximately 4 ft long glass column containing multiple oblique mesh baffles through which ethanol vapor is circulated. To begin a "run," about 100 flies are introduced into the top of the inebriometer. With time, flies lose their ability to stand on the baffles and gradually tumble downward. As they fall out of the bottom of the inebriometer, a fraction collector is used to gather them at 3 min intervals, at which point they are counted. The elution profile of wild-type control flies follows a normal distribution; the mean elution time (MET), approximately 20 min at a standard ethanol vapor concentration, is inversely proportional to their sensitivity to ethanol (Moore, 1998).

A genetic screen was carried out to isolate P element-induced mutants with altered sensitivity to ethanol intoxication using the inebriometer as the behavioral assay. One X-linked mutation isolated in this screen was named cheapdate (chpd) to reflect the increased ethanol sensitivity displayed by hemizygous mutant male flies. chpd males elute from the inebriometer with a MET of 15 min compared with 20 min for the wild-type controls. This increased ethanol sensitivity of chpd males was observed at all ethanol vapor concentrations tested. Genetic and molecular analyses reveals that cheapdate is an allele of the memory mutant amnesiac. amnesiac has been postulated to encode a neuropeptide that activates the cAMP pathway. Consistent with this, it has been found that the enhanced ethanol sensitivity of cheapdate can be reversed by treatment with agents that increase cAMP levels or PKA activity. Conversely, genetic or pharmacological reduction in PKA activity results in increased sensitivity to ethanol (Moore, 1998).

Flies carrying mutations in three molecules involved in cAMP signaling were tested for response to ethanol: (1) rutabaga (rut), encoding the Ca2+-calmodulin-sensitive AC; (2) dunce (dnc), encoding the major cAMP-phosphodiesterase (PDE), and (3) DCO, encoding the major catalytic subunit of cAMP-dependent protein kinase (PKA-C1). Males hemizygous for rut mutations display an ethanol-sensitive phenotype similar to that of amn mutants. Flies heterozygous for the loss-of-function DCO alleles, which show reduced cAMP-stimulated PKA activity, also display increased ethanol sensitivity (homozygotes cannot be tested because they die as embryos). Ethanol sensitivity of males hemizygous for dnc mutations, however, are nearly normal. These data show that flies unable to increase cAMP levels normally (such as rut and possibly amn) or to respond properly to increased cAMP levels (such as DCO/+) are more sensitive to ethanol-induced loss of postural control. The converse, however, is not observed; dnc flies, whose cAMP levels are several times higher than wild type, display nearly normal ethanol sensitivity, a phenotype that is also observed in males doubly mutant for dnc and amn. Unexpectedly, whereas both rut and amn are ethanol sensitive, males doubly mutant for rut and amn are not significantly different from control (Moore, 1998).

To further investigate the relationship between cAMP signaling and ethanol sensitivity, the adenylyl cyclase (AC) activator forskolin was used to manipulate cAMP levels in adult flies. Control and amnchpd males were fed a 10 µM forskolin solution for 2 or 4 hr prior to assaying their ethanol sensitivity in the inebriometer. Whereas forskolin treatment has no effect on the behavior of control flies, the ethanol sensitivity defect of amnchpd flies is reversed by a 2 hr forskolin treatment. Likewise, treatment of rut1 males with forskolin for 2 hr leads to normal ethanol sensitivity, a result likely due to the activation of another AC. Interestingly, a 4 hr forskolin treatment of amnchpd males further reduces ethanol sensitivity, suggesting that one or more components of the cAMP pathway may have undergone compensatory up-regulation in amnchpd mutants, thereby increasing the system's ability to respond to pharmacologically induced increases in cAMP levels. Taken together, these data indicate that the effects of amn and rut on ethanol sensitivity are directly related to their ability to modulate cAMP levels (Moore, 1998).

A reduction of PKA-C1 function, as observed in males heterozygous for DCO alleles, leads to increased ethanol sensitivity. To corroborate a role for PKA in ethanol sensitivity, adult control and amnchpd males were fed solutions containing 200 µM Rp-cAMPS or Sp-cAMPS for 2 hr prior to their assay in the inebriometer. Rp-cAMPS is a competitive antagonist of cAMP that binds the regulatory subunit of PKA without releasing the catalytic subunit; Sp-cAMPS is an analog of cAMP that activates PKA. Sp-cAMPS treatment of control males does not alter ethanol sensitivity. This treatment, however, completely reverses the enhanced ethanol sensitivity of amnchpd. In contrast, feeding Rp-cAMPS to control males results in increased ethanol sensitivity. Rp-cAMPS treatment has the opposite effect on amnchpd males, partially reversing their increased ethanol sensitivity. While unexpected, this last observation is consistent with the finding that flies doubly mutant for rut and amn do not (unlike single mutants) display increased ethanol sensitivity. Treatment of control flies with the PKA inhibitor Rp-cAMPS for only 2 hr leads to an ethanol-sensitive phenotype similar to that of amn, rut, and DCO/+ flies. This argues that even a relatively short-term inhibition of the cAMP pathway is sufficient to increase ethanol sensitivity (Moore, 1998).

In mammalian cells and tissues, ethanol potentiates receptor-mediated cAMP signal transduction; the mechanisms underlying this effect, however, remain poorly understood. While a direct link between cAMP signaling and ethanol-induced behaviors has not been established in mammals, the responses to acute ethanol are thought to be mediated by alterations in the function of various ligand-gated ion channels. Certain subtypes of GABAA and NMDA receptors are potentiated and inhibited by ethanol, respectively, and both these channels can be phosphorylated by PKA in cells, tissues, or heterologous expression systems. It is tempting to speculate that PKA phosphorylation of neurotransmitter receptors is altered by ethanol and that this contributes to the behavior of the inebriated animal (Moore, 1998 and references).

Induction of cAMP response element-binding protein-dependent medium-term memory by appetitive gustatory reinforcement in Drosophila larvae: larval memory depends on both amnesiac and CREB

Drosophila has been successfully used as a model animal for the study of the genetic and molecular mechanisms of learning and memory. Although most of the Drosophila learning studies have used the adult fly, the relative complexity of its neural network hinders cellular and molecular studies at high resolution. In contrast, the Drosophila larva has a simple brain with uniquely identifiable neural networks, providing an opportunity of an attractive alternative system for elucidation of underlying mechanisms involved in learning and memory. This paper describes a novel paradigm of larval associative learning with a single odor and a positive gustatory reinforcer, sucrose. Mutant analyses have suggested importance of cAMP signaling and potassium channel activities in larval learning as has been demonstrated with the adult fly. Intriguingly, larval memory produced by the appetitive conditioning lasts medium term and depends on both amnesiac and cAMP response element-binding protein (CREB). A significant part of memory was disrupted at very early phase by CREB blockade without affecting immediate learning performance. Moreover, synaptic output of larval mushroom body neurons is required for retrieval but not for acquisition and retention of the larval memory, including the CREB-dependent component (Honjo, 2005).

The larval olfactory system is significantly simpler than the adult system with only 21 odorant receptor neurons. To find chemicals that are suitable for larval learning assays, 30 odorants were examined for naive larval chemotactic behavior and they were classified into four groups based on their attractiveness. 19 moderate attractants were examined for their effectiveness on larval appetitive olfactory conditioning. Larvae were exposed to an odor for 30 min in association with 1 M sucrose spread on agar. After conditioning, larvae were gently rinsed with distilled water to remove sucrose and tested for olfactory response on the test plate. For 10 of the 19 odorants, animals that received the odor with 1 M sucrose showed enhanced migration to the conditioned odor with significantly higher RI than control larvae, which had been exposed to the same odor but in conjunction with distilled water. Among the odorants examined, linalool (LIN), Pentyl acetate (PA), and gamma-valerolactone (GVA), which gave the largest RI increments in LIN/SUC conditioning, were chosen (Honjo, 2005).

To examine whether the increase of response index after conditioning is attributable to associative learning, a set of control experiments were performed. Significant response index increase was observed only when larvae were trained with LIN in association with SUC (LIN/SUC); response index did not change significantly from naive larvae when larvae are trained with LIN in association with distilled water (LIN) or sucrose alone (SUC). Notably, neither LIN nor sucrose alone resulted in habituation of larval olfactory responses compared with naive animals. Similar results were obtained with PA, except that conditioning with PA in association with distilled water led to slight desensitization. In contrast, conditioning with GVA in association with distilled water led to strong desensitization. However, the associative conditioning with GVA/SUC overcame the suppression (Honjo, 2005).

It was then asked whether the enhancement of larval response requires simultaneous exposure to both the odor and the reinforcer. As a temporal dissociation control, larvae were successively exposed first to sucrose and then to LIN or vise versa. Whereas simultaneous exposure to both LIN and sucrose (conditioning 1) resulted in enhanced olfactory response, the dissociation control, in which larvae were first exposed to sucrose and then to LIN, led to no enhancement compared with the odor alone control (conditioning 2). The requirement of temporal association between odor exposure and sucrose reinforcement was further confirmed in another set of dissociation controls. Exposure to LIN (conditioning 5) led to slightly higher larval response than conditioning 2, which seems a nonassociative effect caused by the delay attributable to the 30 min mock treatment (for delayed nonassociative effects). Nonetheless, simultaneous exposure to LIN and 1 M sucrose (conditioning 4) led to additional response index increment reproducing associative odor learning. In contrast, separate exposures to LIN and then 1 M SUC (conditioning 6) failed to do so (Honjo, 2005).

It was next asked whether the increased larval olfactory response was specific to the exposed odor. To address this question, larval olfactory responses were tested using odorants other than the one used for conditioning. When larvae were trained with LIN/SUC, PA/SUC, or GVA/SUC, only those trained with LIN/SUC showed significant response index increment in the olfactory test with LIN. Similarly, only larvae trained with PA/SUC showed significant response index increment in the olfactory test with PA. These results thus demonstrate that the enhanced larval response with sucrose is specific to the conditioned odor and suggest that Drosophila larvae discriminate the three odors despite their limited olfactory system (Honjo, 2005).

Whereas the above data emphasizes the importance of sucrose as a positive reinforcer, it is not clear whether response index stimulation is attributable to gustatory stimuli or attributable to higher osmotic pressure of 1 M sucrose than that of distilled water. To clarify this point, larvae were trained with LIN in association with 1 MD-sorbitol, a sugar that is tasteless to the flies. Conditioning with LIN in association with D-sorbitol failed to stimulate larval response index compared with the control, in which larvae were exposed to LIN in association with distilled water (Honjo, 2005).

Most studies on Drosophila associative learning have used reciprocal and symmetrical experimental paradigms with two odors. In contrast, the paradigm here uses only a single odor for conditioning and test. Consequently, this asymmetric nature calls for parallel controls to rule out nonassociative learning such as habituation and sensitization. Nonetheless, the paradigm resulted in significant learning only by the associative conditioning, in which both an odor and sucrose were simultaneously presented to larvae; enhanced larval olfactory response was specific to the odor paired with sucrose, excluding nonassociative sensitization to a broad range of odors. Conversely, it should be noted that strong desensitization was observed for certain odors such as GVA. Even with LIN, which showed no desensitization in immediate learning, delayed nonassociative effects on larval olfactory response were detected, emphasizing the importance of odor choice and careful data interpretation (Honjo, 2005).

Because different sets of larvae are used for control experiments for the stimuli involved, reproducibility of larval responses is critical to the paradigm. At this point, select odorants were used for screened for larval olfactory learning. Thus, of 30 chemicals, several odorants were chosen that produced significant response index increment with sucrose. Many odorants, such as 1-octanol and 4-methylcyclohexanol, which have been used in adult studies, failed to produce significant response index increment. The fact that larvae and adult flies exhibit different olfactory responses also highlights the importance of odorant choice for larval experiments (Honjo, 2005).

Despite its asymmetric design, several points are notable with regard to this paradigm: (1) the simple experimental design minimizes stress on larvae, which could affect learning performance; (2) the paradigm generates medium term memory (MTM) that lasts up to 3 h; (3) the paradigm is free from odor discriminative task. Because the larval olfactory system is considerably simpler than the adult system, simultaneous discrimination of different odors could complicate animal responses, although other studies have used two-odor paradigms; (4) because only a single odor is applied to larvae during training, the simple design of this paradigm may be of use in imaging of neural representation of the conditioned odor in the brain during learning and memory (Honjo, 2005).

Adult flies with amn mutations show a reduction in immediate memory as well as a more profound reduction in MTM. In this paradigm, amn larvae show reduced but significant immediate learning/memory. In the adult brain, the AMN peptide is expressed in dorsal paired medial (DPM) neurons that are situated medially to MBs and ramify throughout the MB lobes. Little is known about the network of the DPM neurons and the AMN expression pattern in the larval brain (Honjo, 2005).

Studies with Aplysia, mice, and adult Drosophila flies show that CREB-dependent transcription is required for cellular events underlying LTM. These studies have shown that CREB functions as a conserved molecular switch for LTM, which is thought to be induced several hours after training. Moreover, intervals between trainings or stimulations are generally required to produce CREB-dependent long-term effects (Honjo, 2005).

The larval CREB-dependent memory is stable for only medium term. Moreover, this paradigm continuously exposes larvae to an odor and sucrose during training, a condition similar to massed training of adult flies. Intriguingly, CREB is recruited shortly after learning in larvae; a significant portion of 30 min memory was disrupted by the CREB blocker, whereas immediate learning was not. If the larval MTM is induced after STM as in the adult fly, this very early CREB requirement might imply fast transition of memory phases. Alternatively, the CREB-dependent memory might also be generated independently. Intriguingly, it has been proposed that CREB can be activated independent of STM in long-term synaptic facilitation in Aplysia. In addition, although memory performance becomes undetectable in 3 h, the requirement of CREB activity suggests neural mechanisms that are in part shared with LTM in the adult fly. In fact, memory decay after CREB blockade is somewhat slower than in amn mutants. Furthermore, whereas CREB blocker has been shown to suppress 1 and 7 d memories, whether the blockade has more immediate effects is not known, leaving the possibility that CREB could be recruited early in the adult fly as well. Notably, memory performance in the adult fly tends to be higher with spaced training than with massed training already at several hours (Honjo, 2005).

Biochemically, CREB is activated by phosphorylation in response to diverged extra cellular stimuli. Among them, the protein kinase A (PKA) plays a central role in phosphorylation of CREB1-a, the catalytic subunit. Because the larval memory is completely disrupted in dnc and rut mutants, the cAMP-PKA pathway might be involved in the early activation of CREB in larvae. Alternatively, intracellular pathways other than PKA could also be recruited to mediate CREB activation. Intriguingly, increase of intracellular cAMP is known to activate mitogen-activated protein kinase in Aplysia, which in turn phosphorylates CREB2-b, the regulatory subunit, allowing transcriptional activation by the catalytic CREB isoform in the nuclei (Honjo, 2005).

The adult MBs are highly complex structures with three sets of lobes, each of which might participates in different memory traces. In contrast, the larval MBs exhibit a remarkably simple projection pattern with only a single set of lobes. In addition, recent studies have revealed straightforward organization of the larval olfactory system with only 21 olfactory receptor neurons targeting the 21 antennal lobe glomeruli, from which projection neurons target the larval MB calyx that consists of ~28 glomeruli (Honjo, 2005).

The finding that larval MB output is essential for memory retrieval discloses functional importance of the larval MBs and directly demonstrates anatomical commonality of memory networks between the larval and adult brains. Furthermore, the results that larval MB output is not required for memory acquisition and retention suggest that larval olfactory memory is localized upstream of larval MB synapses, in either MB neurons themselves or upstream circuits such as antennal lobes. Combined with the recent advances in functional neural imaging, the simple and identifiable neural network of the larval olfactory system will help further elucidation of the cellular basis of learning and memory in the brain (Honjo, 2005).

A single pair of neurons modulates egg-laying decisions in Drosophila

Animals have to judge environmental cues and choose the most suitable option for them from many different options. Female fruit flies selecting an optimum site to deposit their eggs is a biologically important reproductive behavior. When given the direct choice between ovipositing their eggs in a sucrose-containing medium or a caffeine-containing medium, female flies prefer the latter. However, the neural circuits and molecules that regulate this decision-making processes during egg-laying site selection remain poorly understood. The present study found that amnesiac (amn) mutant flies show significant defects in egg-laying decisions, and such defects can be reversed by expressing the wild-type amn transgene in two dorsal paired medial (DPM) neurons in the brain. Silencing neuronal activity with an inward rectifier potassium channel (Kir2.1) in DPM neurons also impaired egg-laying decisions. Finally, the activity in mushroom body αβ neurons was required for the egg-laying behavior, suggesting a possible 'DPM-αβ neurons' brain circuit modulating egg-laying decisions. These results highlight the brain circuits and molecular mechanisms of egg-laying decisions in Drosophila (Wu, 2015).

amn encodes a preproneuropeptide with limited similarity to pituitary-adenylyl-cyclase-activating peptide (PACAP). It has been reported that AMN plays a critical role in behaviors of Drosophila such as olfactory memory and sleep (Liu, 2008). To examine the role of the amn gene in egg-laying decisions, a collection of amn mutants were analyzed for their egg-laying preference in the behavioral chambers. Interestingly, amn1, amn28A, amnc651, and amnX8 mutants showed significant defects in egg-laying preference compared to wild-type flies. The egg-laying preference was further examined in the chamber containing sucrose or caffeine substrate in one side and a plain substrate in the opposite side. Consistent with the previous findings, wild-type female flies avoided laying eggs on sucrose or caffeine substrates when the other option was a plain substrate. All the amn mutants show significant difference in egg-laying preference in sucrose/plain or caffeine/plain chambers compared to wild-type flies. These results indicate the amn gene is critical for egg-laying decisions in sucrose/caffeine, sucrose/plain, and caffeine/plain mediums (Wu, 2015).

Although the amn gene is expressed throughout the fly brain, targeting expression of the amn gene in two DPM neurons restores the olfactory memory in amn mutant flies (Waddell, 2000). Tests were performed to see whether the amn gene product in DPM neurons is involved in egg-laying decisions. A GAL4/UAS system was used to target expression of the wild-type amn transgene (amn+) in DPM neuron by applying three independent DPM specific GAL4 drivers, the C316-GAL4, VT6412-GAL4, and VT64246-GAL4. amn1 is an EMS-induced mutation in the allele of the amn gene that causes a significant reduction in the amn transcript. Therefore, amn1 was chosen to perform the following rescue experiment. Flies carrying the amn1/amn1; +/+; C316-GAL4/UAS-amn+, or amn1/amn1; +/+; VT6412-GAL4/UAS-amn+, or amn1/amn1; +/+; VT64246-GAL4/UAS-amn+ showed normal egg-laying preferences compared to wild-type flies, indicating that targeting expression of the amn transgene in DPM neurons restored typical egg-laying preference. In addition, acute silencing of the neuronal activity in DPM neurons by an inward rectifier potassium channel (Kir2.1) disrupts egg-laying preferences, suggesting a role of neurotransmission in DPM neurons for execution of normal egg-laying preference (Wu, 2015).

The fibers of DPM neurons innervate the mushroom body, and both axons and dendrites are evenly distributed in the lobes and the anterior peduncle of the mushroom body. Therefore, the role of the mushroom body neurons was examined in egg-laying preferences of female flies. The Drosophila mushroom body consists of 2000 neurons in each hemisphere of the brain, and the neurons in the mushroom body can be classified into the γ, α'β', and αβ subsets. The effects were examined of acute inhibition of activity in different subsets of mushroom body neurons by tubP-GAL80ts; UAS-Kir2.1 combined with R16A06-GAL4 (γ neurons) or VT30604-GAL4 (α'β' neurons) or VT49246-GAL4 (αβ neurons. Surprisingly, only inhibiting the neuronal activity in the αβ neurons disrupted the normal female egg-laying preference. These data suggest that the release of the AMN neuropeptide from DPM neurons onto the mushroom body αβ neurons regulates egg-laying preference in female flies (Wu, 2015).

The egg-laying site selection by female fruit flies provides a suitable system to study the cellular mechanisms of a simple decision-making behavior. When given the direct choice between a sucrose-containing medium and a caffeine-containing medium, flies prefer to lay eggs on the latter. This decision-making process during egg-laying site selection is unchanged in aged animals, suggesting that aging does not dramatically alter the neural activity involved in egg-laying decisions (Wu, 2015).

amn1 is the first amnesiac mutant isolated from the behavioral screening for olfactory memory mutants. This study has identified the crucial role of the amn gene on egg-laying decisions in female flies. The egg-laying preference is altered in amn1, amn28A, and amnC651, and amnX8 mutants compared to wild-type flies, implying that the amn gene product is important for normal egg-laying decisions. Interestingly, it was observed that the amnX8 showed significant difference in egg-laying preference in sucrose/caffeine or sucrose/plain medium compared to the other amn mutants. The original amn1 is an EMS-induced mutant allele in the amn gene while amn28A and amnc651 are P-element-induced mutations in the amn gene. The amnX8 was made by imprecise excision of the P-element from amn28A, and a significant increase in ethanol-sensitive phenotype was found in amnX8 compared to amn1 and amn28A. It is noteworthy that amnX8 contains possibly other GAL4 insertions elsewhere in the genome left after excision of amn28A, which may cause a significant negative value of egg-laying preference index in sucrose/caffeine medium. Genetic expression of the wild-type amn transgene in DPM neurons of amn1 mutant flies restores the deficiency of egg-laying preference, suggesting that the expression of AMN in DPM neurons is sufficient for normal egg-laying decisions. The AMN neuropeptide is a homologue of the vertebrate PACAP that mediates several physiological functions through stimulation of cAMP production, implying that the cAMP-signaling pathway is important for decision-making processes during egg-laying site selection in Drosophila (Bhattacharya, 2004; Wu, 2015 and references therein).

Both the axons and dendrites of DPM neurons are evenly distributed in different lobes of the mushroom body, suggesting that DPM neurons receive from and transmit to the mushroom body. It has been reported that the neurotransmissions from DPM or mushroom body α'β' neurons are required for olfactory memory consolidation. In addition, the projections of DPM neurons to the α'β' lobes of the mushroom body are sufficient for stabilizing olfactory memory. These data suggest the possible reciprocal feedback circuits between DPM-mushroom body α'β' neurons for olfactory memory consolidation. The current data indicate that AMN release from DPM neurons is critical for normal egg-laying decisions. Silencing the activity in mushroom body αβ neurons also affects this behavior, suggesting that the neural circuitry downstream of DPM neurons modulates egg-laying decisions. However, the neural activity in mushroom body α'β' neurons is not required for normal egg-laying decisions, which indicates the involvement of separate subsets of mushroom body neuron during olfactory memory consolidation and egg-laying decisions. In addition to the AMN neuropeptide, it has been shown that DPM neurons also release serotonin (5HT) onto the mushroom body αβ neurons via the action of the 5HT1A receptor. Whether 5HT and the 5HT1A receptor are required for egg-laying decisions is still unknown (Wu, 2015).

Interestingly, a recent study identified that different subsets of dopaminergic neurons play opposing roles in egg-laying preference on ethanol substrate in a concentration-dependent manner (Azanchi, 2013). Neuronal activity in the mushroom body α'β' neurons and the ellipsoid body R2 neurons is also required for normal egg-laying preference for ethanol in female flies (Azanchi, 2013). It is speculated that egg-laying decisions on different substrates (i.e. different concentrations of ethanol-containing foods or sucrose/caffeine containing medium) are mediated by independent subsets of mushroom body neurons. Further study is needed to establish the molecular and neural circuits in the mushroom body involved in decision-making processes during egg-laying site selection in Drosophila (Wu, 2015).


Amino Acids 170

Structural Domains

Amnesiac has an N-terminal signal peptide that functions in protein secretion and four putative dibasic cleavage sites whereby the protein could be cleaved into peptides (Feany, 1995).

amnesiac: Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References

date revised: 10 May 2006

Home page: The Interactive Fly © 2006 Thomas Brody, Ph.D.

The Interactive Fly resides on the
Society for Developmental Biology's Web server.