Abstract
The laterodorsal tegmentum (LDT) is associated with reward considering that it modulates VTA neuronal activity, but recent anatomical evidence shows that the LDT also directly projects to nucleus accumbens (NAc). We show that the majority of LDT-NAc inputs are cholinergic, but there is also GABAergic and glutamatergic innervation; activation of LDT induces a predominantly excitatory response in the NAc. Non-selective optogenetic activation of LDT-NAc projections in rats enhances motivational drive and shifts preference to an otherwise equal reward; whereas inhibition of these projections induces the opposite. Activation of these projections also induces robust place preference. In mice, specific activation of LDT-NAc cholinergic inputs (but not glutamatergic or GABAergic) is sufficient to shift preference, increase motivation, and drive positive reinforcement in different behavioral paradigms. These results provide evidence that LDT-NAc projections play an important role in motivated behaviors and positive reinforcement, and that distinct neuronal populations differentially contribute for these behaviors.
Highlights
The laterodorsal tegmentum (LDT) is associated with reward considering that it modulates ventral tegmental area (VTA) neuronal activity, but recent anatomical evidence shows that the LDT directly projects to nucleus accumbens (NAc)
To confirm previous findings showing that LDT sends direct projections to NAc16, we injected in the NAc of rats an adeno-associated virus (AAV5) containing a vector encoding for wheat germ agglutinin cre fusion protein (AAV5–EF1a–WGA–Cre–mCherry) in combination with injection in the LDT of cre-dependent channelrhodopsin (AAV5-Ef1a-DIO-hChR2(H134R)-eYFP) (Fig. 1a)
50% of YFP-transfected LDT neurons were cholinergic, 29% glutamatergic, and 23% GABAergic (Fig. 1d, e); in line with previous observations showing that 59–74% of LDT-NAc projections were cholinergic16
Summary
The laterodorsal tegmentum (LDT) is associated with reward considering that it modulates VTA neuronal activity, but recent anatomical evidence shows that the LDT directly projects to nucleus accumbens (NAc). We show that the majority of LDT-NAc inputs are cholinergic, but there is GABAergic and glutamatergic innervation; activation of LDT induces a predominantly excitatory response in the NAc. Non-selective optogenetic activation of LDT-NAc projections in rats enhances motivational drive and shifts preference to an otherwise equal reward; whereas inhibition of these projections induces the opposite. Non-selective optogenetic activation of LDT-NAc projections in rats enhances motivational drive and shifts preference to an otherwise equal reward; whereas inhibition of these projections induces the opposite Activation of these projections induces robust place preference. Specific activation of LDT-NAc cholinergic inputs (but not glutamatergic or GABAergic) is sufficient to shift preference, increase motivation, and drive positive reinforcement in different behavioral paradigms. We observed that non-selective optogenetic activation of LDT-NAc projections was sufficient to increase motivation, induce preference and positive reinforcement in rats, whereas inhibition produced the opposite outcome. We further showed that most of these effects were mediated by LDT-NAc cholinergic inputs, whereas optical modulation of glutamatergic and GABAergic inputs originated different behavioral outcomes
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