Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics

Abstract

Animals employ diverse learning rules and synaptic plasticity dynamics to record temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso and Rubin, 2016). Here, we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in Drosophila. NO’s effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.

The connectome of the adultDrosophilamushroom body: implications for function

“…DANs have been traditionally grouped into two clusters, PPL1 and PAM, based on the position of their cell bodies ( Figure 6). PPL1 DANs innervate the vertical lobes and generally convey punishment, whereas PAM DANs innervate horizontal lobes and generally convey reward (Aso et al, 2019(Aso et al, , 2012(Aso et al, , 2010Aso and Rubin, 2016;Burke et al, 2012;Claridge-Chang et al, 2009;Felsenberg et al, 2018Felsenberg et al, , 2017Huetteroth et al, 2015;Jacob and Waddell, 2020;Lin et al, 2014b;Liu et al, 2012;Mao and Davis, 2009;Schwaerzel et al, 2003). There is also a DAN from the PPL2ab cluster, PPL201 (Figure 3-figure supplement 1G), that innervates the CA (Mao and Davis, 2009;Tanaka et al, 2008;Zheng et al, 2018) and has been reported to play a role in signalling saliency (Boto et al, 2019).…”

“…There are established cases of glutamate having inhibitory (Liu and Wilson, 2013) and excitatory (Johansen et al, 1989) action. Most cells appear to express both inhibitory and excitatory receptors for glutamate; for example, all six MBON and all ten DAN cell types for which data exists express both inhibitory GluClalpha and excitatory NMDA type receptors (Aso et al, 2019). Activation of cholinergic and glutamatergic MBONs has been associated with opposing behaviors, avoidance and approach, respectively (Aso et al, 2014b;Owald et al, 2015;Perisse et al, 2016), but the extent to which these result from the action of these MBONs on shared targets has not been established.…”

“…A large body of evidence indicates that these anatomically defined compartments of the MB are the units of associative learning (Aso et al, 2012(Aso et al, , 2010(Aso et al, , 2019(Aso et al, , 2014a(Aso et al, , 2014bAso and Rubin, 2016;Berry et al, 2018;Blum et al, 2009;Bouzaiane et al, 2015;Burke et al, 2012;Claridge-Chang et al, 2009;Isabel et al, 2004;Jacob and Waddell, 2020;Krashes et al, 2009; S. Lin et al, 2014;Liu et al, 2012;Owald et al, 2015;Pai et al, 2013;Plaçais et al, 2013;Schwaerzel et al, 2003;Séjourné et al, 2011;Trannoy et al, 2011;Yamagata et al, 2015;Zars et al, 2000).…”

“…These differences between DAN cell types presumably reflect in large part the nature of the inputs that each DAN receives, but our knowledge of these inputs is just emerging (Otto et al, 2020) and is far from comprehensive. DANs adjust synaptic weights between KCs and MBONs with cell type-specific rules and, in at least some cases, these differences arise from the effects of co-transmitters (Aso et al, 2019). In general, a causal association of KC responses with the activation of a DAN in a compartment results in depression of the synapses from the active KCs onto MBONs innervating that compartment (Hige et al, 2015;Handler et al, 2019).…”

Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior

“…What might be the neuronal subsets that produce NO and regulate period length of locomotor activity? A recent study by the group of Y. Aso and G. Rubin [54], has shown that NO acts as a co-transmitter in a subset of dopaminergic neurons, specifically in some of the PAMs, PPL1s and PPL2abs. It is thus possible that dopamine signaling modulated by NO is involved in the control of the locomotor activity period.…”