Relation of Locus Coeruleus Neurons in Monkeys to Pavlovian and Operant Behaviors

Abstract

Bouret S, Richmond BJ. Relation of locus coeruleus neurons in monkeys to Pavlovian and operant behaviors. J Neurophysiol 101: 898 -911, 2009. First published December 17, 2008 doi:10.1152/jn.91048.2008. Noradrenaline is released throughout the forebrain from locus coeruleus (LC) projections in close temporal proximity to emotional and goal-directed events. To examine interactive influences of these processes on LC neuronal activity, we used a task where Pavlovian and operant processes vary and can be easily identified. We recorded 69 single LC neurons from two monkeys performing a task where cues indicate the progression through schedules of one, two, or three operant trials. Pavlovian responses and phasic LC activations occur following the appearance of conditioned visual cues (54/69 neurons), especially those at the beginning of new schedules, whether the current trial will be rewarded (single trial schedule) or not (2 or 3 trial schedules), and after visual imperative signals eliciting the operant response (64/69 neurons), whether the current trial will be rewarded or not. The modulation of LC responses seems to be relatively independent of attention or motivation, because the responses do not covary with operant performance in the task. The magnitude of LC responses across the schedules varied in close relation to the intensity of Pavlovian behavior but these responses were also modulated by operant processes. Our conclusion is that LC activation occurs when task-relevant stimuli evoke a conditioned instinctive (Pavlovian) response, with the strength of the activation also being modulated by goal-directed processes. Thus locus coeruleus neurons broadcast information about stimulus-elicited primitive and goal-directed behaviors to forebrain structures important for executive functions and emotions.

Mechanisms underlying memory enhancement in humans

“…These results suggest that the action evoked memory enhancement is mediated by a possible LC and parahippocampal gyrus circuit underlying. NE release can be triggered by the action, as has been previously shown in animal studies (Bouret & Richmond, 2009;Bouret & Richmond, 2015;Kalwani et al, 2014;Pavlenko & Kulichenko, 2003;Varazzani et al, 2015), reaching MTL target areas promoting memory formation LaBar & Cabeza, 2006;McGaugh, 2000McGaugh, , 2004Strange et al, 2003;Tully et al, 2010). Emotional arousal has been shown to enhance episodic memory via 2 -28 -16; Z = 3.38; p<0.001 unc.…”

“…Strikingly this LC response was shown to be better aligned to the movement compared to the stimuli presentation in and was not elicited either in the present of a response inhibition cue, or with the successful withholding of the movement (Kalwani et al, 2014). Interestingly, this LC response is elicited regardless of speed of response (Bouret & Richmond, 2009;Bouret & Richmond, 2015;, correctness Kalwani et al, 2014) or reward expectation -LC fires with action even when the animal did not anticipate reward- (Bouret & Richmond, 2015;Clayton et al, 2004). Furthermore the anticipation of effort needed to perform an action has been also shown to modulate LC firing suggesting that LC is also signalling the energy requirements of the movement (Varazzani et al, 2015).…”

“…There are several studies showing LC phasic activation aligned to both the onset of the stimulus presentation and voluntary movement response (Bouret & Richmond, 2009;Clayton et al, 2004;Kalwani et al, 2014). Strikingly this LC response was shown to be better aligned to the movement compared to the stimuli presentation in and was not elicited either in the present of a response inhibition cue, or with the successful withholding of the movement (Kalwani et al, 2014).…”

“…They concluded LC phasic activation corresponded to the reward-driven decision to act, but not the reward-driven decision not to act. Bouret and Richmond (2009) showed in a rewarded operant task, where monkeys were instructed to touch a bar after a go signal, that LC phasic activation is locked to the bar release (Go response) for the reward, to the go signal cue appearance on the screen and that this firing pattern was not affected by the reaction times (Bouret & Richmond, 2009). They later performed a similar experiment with 3 different conditions: (1) active trials where a cue indicating the size of the reward was presented and then a bar had to be released after the go signal cue, (2) passive trials where the cue was presented indicating reward size but no action were required (2s after the onset of the cue the reward was given) and (3) self-initiated trials where no cue was presented and touch and release of the bar was required to receive the reward.…”

“…Recent single-unit recordings of the LC in non-human primates demonstrate increased activity before the onset of the movement or with the onset of the stimuli presentation led to the suggestion that LC phasic response is driven by the outcome of a decision process and the commitment to act (Bouret, & Richmond, 2009;Bouret & Richmond, 2015;Clayton et al, 2004;Kalwani et al, 2014;Pavlenko & Kulichenko, 2003;Varazzani et al, 2015). It could be possible that later components of the LC activation would produce NE liberation after motor circuits are already activated.…”