Abstract
The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain. The LHb is known to modulate midbrain dopamine (DA) neurons, including inhibition of ventral tegmental area (VTA) neurons via glutamatergic excitation of the GABAergic rostromedial tegmental nucleus (RMTg). A variety of lines of evidence show activity in LHb and the LHb-RMTg pathway is correlated with, and is sufficient to support, punishment learning. However, it is not immediately clear whether LHb is necessary for punishment. Here we used a within-subjects punishment task to assess the role of LHb in the acquisition and expression of punishment as well as in aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of an AMPA receptor antagonist (NBQX) into LHb had no effect on the acquisition or expression of this punishment, or on aversive choice, but did increase locomotion. Infusion of the sodium channel blocker bupivacaine likewise had no effect on expression of punishment. However, infusion of the calcium channel blocker mibefradil did affect expression of punishment by significantly decreasing the latency with which rats responded on the punished lever and significantly increasing unpunished lever-pressing. Taken together, these findings indicate that the LHb plays a limited role in punishment, influencing only latency to respond. This role is linked to calcium channel permeability and not AMPA receptor or sodium channel permeability.
Highlights
The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain [1]
There was no effect of NBQX infusions on lever-press latencies (all F(1,5),1.2; p..05). These results show that AMPA receptor antagonism in LHb has no significant effect on aversive choice
NBQX infusions into the LHb significantly increased locomotor activity as measured by total distance travelled (F(1,15) = 21.6; p,.05) (Figure 5C) and velocity (F(1,15) = 18.4; p..05) (Figure 5D). This experiment studied the role of the LHb in punishment by reversibly inactivating the LHb, using NBQX, during various punishment-influenced tasks
Summary
The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain [1]. Recording studies in rhesus monkeys have shown that LHb and RMTg neurons are phasically excited by unexpected aversive events and reward omissions, as well as by cues that predict those outcomes. These phasic excitations are closely followed by a phasic inhibition of midbrain DA neuronal firing [2]. These results have been interpreted as LHb neuronal coding of aversive outcome values and suppressing motor behavior and reward seeking. Stamatakis and Stuber [8] reported that ChR2 stimulation of LHb terminals in the RMTg supported both active and passive place avoidance learning in mice, and negatively reinforced as well as positively punished nosepoking behaviour in mice
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