Eric M. Bowman

Rodent models of prefrontal cortical function

In this article, we consider whether studies in rats can provide useful information regarding the debate about the functions of the primate prefrontal cortex. At a superficial level, comparison of regional specializations within the prefrontal cortices of different species suggests functional correspondence. Unfortunately, the nature of functional specialization in primate prefrontal cortex is controversial, and data supporting the idea of homology between specific areas of rat and primate prefrontal cortex are weak. Nevertheless, we argue here that studies of the computational functions within the relatively undifferentiated prefrontal cortex of rats can shed light on processing in primate prefrontal cortex.

Recordings from the rat locus coeruleus during acute vagal nerve stimulation in the anaesthetised rat

Vagal nerve stimulation (VNS) is used as a treatment for Epilepsy and is currently under investigation as a treatment for depression (see [M.S. George, Z. Nahas, X. Li, F.A. Kozel, B. Anderson, K. Yamanaka, J.H. Chae, M.J. Foust, Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS), Semin. Clin. Neuropsychiatry 7 (2002) 293-304; M.S. George, A.J. Rush, H.A. Sackeim, L.B. Marangell, Vagus nerve stimulation (VNS): utility in neuropsychiatric disorders, Int. J. Neuropsychopharmacol. 6 (2003) 73-83] for reviews). The mechanism of action of VNS is not fully understood [E. Ben-Menachem, Vagus-nerve stimulation for the treatment of epilepsy, Lancet Neurol. 1 (2002) 477-482] despite numerous imaging investigations (see [E. Ben-Menachem, Vagus-nerve stimulation for the treatment of epilepsy, Lancet Neurol. 1 (2002) 477-482; M.S. George, Z. Nahas, X. Li, F.A. Kozel, B. Anderson, K. Yamanaka, J.H. Chae, M.J. Foust, Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS), Semin. Clin. Neuropsychiatry 7 (2002) 293-304; M.S. George, A.J. Rush, H.A. Sackeim, L.B. Marangell, Vagus nerve stimulation (VNS): utility in neuropsychiatric disorders, Int J Neuropsychopharmacol 6 (2003) 73-83; M.S. George, H.A. Sackeim, L.B. Marangell, M.M. Husain, Z. Nahas, S.H. Lisanby, J.C. Ballenger, A.J. Rush, Vagus nerve stimulation. A potential therapy for resistant depression? Psychiatr. Clin. North Am. 23 (2000) 757-783] for reviews). However, there is some evidence to suggest that the locus coeruleus may play a role modulating the effects of VNS. This study investigated the effects of VNS (0.3mA), of sufficient intensity to recruit the A and B fibre components of the vagus [D.M. Woodbury, J.W. Woodbury, Effects of vagal stimulation on experimentally induced seizures in rats, Epilepsia 31 (Suppl. 2) (1990) S7-S19], on the discharge rate of single neurons from the locus coeruleus. This study is the first to demonstrate a direct neuronal response from the locus coeruleus following acute challenge of VNS in the anaesthetised rat. The results of this study indicate that neuronal activity of the locus coeruleus is modulated by VNS. This pathway through the locus coeruleus may be significant for mediating the clinical effects of VNS.

Discriminative Cues Indicating Reward Magnitude Continue to Determine Reaction Time of Rats Following Lesions of the Nucleus Accumbens

The role of the nucleus accumbens in incentive motivation is accepted but poorly understood. In this study, we examined in the rat one aspect of motivated behaviour which might be mediated by the nucleus accumbens, namely the translation of a motivational signal (the expected value of a reward) into motor output (responding for the reward). Rats were trained in a reaction time task in which on each trial they received one, two or three pellets. The number of pellets for each trial was randomly determined in advance and signalled to the rats by cue lights. Rats responded with faster reaction times as the size of the expected reward increased. Following ibotenic acid lesions of the nucleus accumbens, there was no difference in the pattern or the speed of reaction times. Although lesions of the nucleus accumbens did not disconnect the motivational system from the motor system, it is possible that the nucleus accumbens is involved in the learning of the incentive salience of external stimuli. Therefore, after postoperative testing the cue contingencies were reversed. Initially, the cues continued to be interpreted according to their prior significance, but eventually both the lesioned rats and the control group acquired the new relationship and did so in equivalent times. We conclude that the nucleus accumbens is not involved in the acquisition or expression of the processes whereby the expectation of rewards of different value is translated into a motor initiation signal.

Effects of excitotoxic lesions of the rat ventral striatum on the perception of reward cost

Abstract This study examined the possibility that lesions of the nucleus accumbens in rats impair the perception of the ”cost of reward”, as defined by the number of operant responses needed to obtain a food pellet. In a first experiment, visual cues indicated the cost of reward under a multiple-ratio schedule of reinforcement. In a second experiment, the number of lever presses required for each reward incremented with each trial in a progressive-ratio schedule of reinforcement. Lesions of the nucleus accumbens altered the behavioral response to the increasing cost of reward when there was an absence of external cues. There was no change in the ability of the lesioned rats to respond to visual cues that indicated reward availability. The results are considered in terms of the traditional idea of the nucleus accumbens as a limbic-motor interface: it is suggested that, if the nucleus accumbens serves such a function, it is limited to only some contexts.

Wearable organic optoelectronic sensors for medicine

This work was supported by Engineering and Physical Sciences Research Council Programme Grant “Challenging the limits of photonics: Structured light” (grant number EP/J01771X/1) and MRC.

Nucleus accumbens neurons in the rat exhibit differential activity to conditioned reinforcers and primary reinforcers within a second‐order schedule of saccharin reinforcement

The nucleus accumbens has been associated with processing information related to primary reinforcement and reward. Most neurophysiological studies report that nucleus accumbens neurons are phasically excited in response to the onsets of salient events during the seeking of reinforcement and to the delivery of primary reinforcers. However, a minority of studies report inhibition during primary reinforcement. We recorded from 65 neurons in the nucleus accumbens whilst thirsty rats performed under a second‐order schedule of saccharin reinforcement. This allowed us to analyse neural activity and behaviour during reinforcer‐seeking in the presence of conditioned reinforcers (second‐order stimuli, also called ‘conditioned stimuli’), and during primary reinforcer consumption. Specifically, we sought to examine the valence of potential neural responses to primary reinforcement, to compare these responses to second‐order stimulus‐evoked responses, and to determine whether responses were differential to second‐order stimuli presented at different time points within the schedule. Fifty out of 65 neurons we sampled responded to the second‐order stimulus and/or consumption of the primary reinforcer. Most neurons in our sample exhibited excitation following the second‐order stimulus and inhibition to the primary reinforcer, a pattern also present over the average response of the neural population. However, there was no systematic variation in neural responses evoked by second‐order stimuli presented at different temporal proximities to primary reinforcement. Our results provide evidence that partially overlapping mechanisms within the nucleus accumbens differentially process conditioned reinforcers and primary reinforcers.

The effect of systemic d-amphetamine on motor versus motivational processes in the rat

Abstract This study examined the effects of systemic amphetamine in rats performing a reaction time task in which motivation and motor readiness were independently varied. Visual cues indicated the number of trials (one, two or three) needed before reinforcement was made available (i.e., reward cost). Lower reward cost was reflected in both a greater proportion of correctly completed trials and faster reaction times. Reaction times were also shorter as a function of increasing time from start of trial to the onset of the imperative stimulus (foreperiod), reflecting motor readiness or temporal probability summation. It was found that increasing dose of amphetamine resulted in faster reaction times, but the manner in which reaction time was speeded more closely resembled that of motor readiness than it did the speeding due to increasing motivation. Furthermore, the effects on performance of amphetamine and motivational condition were found to be entirely independent: there was no evidence to suggest that amphetamine enhanced, or disrupted, the expectation of forthcoming work or the response vigor which this engenders. It is concluded that systemic amphetamine does not act simply to amplify a natural reward signal. By contrast, amphetamine was found to enhance the effect of foreperiod, suggestive of a mechanism for the psychomotor stimulating effects of amphetamine.

Neurons in dopamine‐rich areas of the rat medial midbrain predominantly encode the outcome‐related rather than behavioural switching properties of conditioned stimuli

Midbrain dopamine neurons are phasically activated by a variety of sensory stimuli. It has been hypothesized that these activations contribute to reward prediction or behavioural switching. To test the latter hypothesis we recorded from 131 single neurons in the ventral tegmental area and retrorubral field of thirsty rats responding during a modified go/no‐go task. One‐quarter (n = 33) of these neurons responded to conditioned stimuli in the task, which varied according to the outcome with which they were associated (saccharin or quinine solution) and according to whether they triggered a switch in the ongoing sequence of the animals behaviour (‘behavioural switching’). Almost half the neurons (45%) responded differentially to saccharin‐ vs. quinine‐conditioned stimuli; the activity of a minority (15%) correlated with an aspect of behavioural switching (mostly exhibiting changes from baseline activity in the absence of a behavioural switch) and one‐third (33%) encoded various outcome–switch combinations. The strongest response was excitation to the saccharin‐conditioned stimulus. Additionally, a proportion (38%) of neurons responded during outcome delivery, typically exhibiting inhibition during saccharin consumption. The neurons sampled did not fall into distinct clusters on the basis of their electrophysiological characteristics. However, most neurons that responded to the outcome‐related properties of conditioned stimuli had long action potentials (> 1.2 ms), a reported characteristic of dopamine neurons. Moreover, responses to saccharin‐conditioned stimuli were functionally akin to dopamine responses found in the macaque and rat nucleus accumbens responses observed within the same task. In conclusion, our data are more consistent with the reward‐prediction than the behavioural switching hypothesis.

Assessment of intradimensional/extradimensional attentional set-shifting in rats

HIGHLIGHTSRats learn novel discriminations based on odours and digging media equally well.Reversal learning is more difficult when attending to odour.Group‐level attentional set‐shifting performance is consistent between tests.Individual‐level attentional set‐shifting performance is not consistent between tests.Rats do not have a ‘flexibility quotient’. ABSTRACT The rat intradimensional/extradimensional (ID/ED) task, first described by Birrell and Brown 18 years ago, has become the predominant means by which attentional set‐shifting is investigated in rodents: the use of rats in the task has been described in over 135 publications by researchers from nearly 90 universities and pharmaceutical companies. There is variation in the protocols used by different groups, including differences in apparatus, stimuli (both stimulus dimensions and exemplars within), and also the methodology. Nevertheless, most of these variations seem to be of little consequence: there is remarkable similarity in the profile of published data, with consistency of learning rates and in the size and reliability of the set‐shifting and reversal ‘costs’. However, we suspect that there may be inconsistent data that is unpublished or perhaps ‘failed experiments’ that may have been caused by unintended deviations from effective protocols. The purpose of this review is to describe our approach and the rationale behind certain aspects of the protocol, including common pitfalls that are encountered when establishing an effective local protocol.

Psychopharmacology of Reward and Appetite in Rats

This article provides an overview of the major neurotransmitters, anatomical structures, and behavioral measures that have been studied in relation to reward and appetite in rodents. The discussion of reward is centered on the role of the dopamine system and on the other neurotransmitter systems that are closely allied with it. The passages covering appetite are based mostly on the functions of neuropeptides and the hypothalamus. Throughout the article, the difficulties of measuring reward and appetite behaviorally are discussed, particularly with regard to confounding variables such as motivation, learning, and nonspecific factors.