Autonomic, behavioral, and neural analyses of mild conditioned negative affect in marmosets.

Abstract

Avoidance and alerting behaviors and accompanying physiological responses, including changes in heart rate (HR), are core components of negative emotion. Investigations into the neural mechanisms underlying the regulation and integration of these responses require animal models that simultaneously measure both the physiological and behavioral components of emotion. A primate model is of particular importance in view of the well developed prefrontal cortex of primates, and this region's critical role in emotion regulation and the etiology of affective disorders. Therefore, we have developed a simple aversive conditioning paradigm to assess, simultaneously, cardiovascular and behavioral responses in the marmoset (Callithrix jacchus). Validation of the paradigm was achieved by (1) comparing conditioned responses to a predictive cue with pseudoconditioned responses to a nonpredictive cue; (2) assessing the acquisition of conditioning following lesions of the amygdala, a region essential for associative learning in humans and rats; and (3) determining the contributions of the sympathetic and parasympathetic nervous system to the conditioned autonomic responses. Marmosets acquired conditioned HR and behavioral responses in the conditioned, but not the pseudoconditioned or amygdala lesioned groups. Conditioned HR accelerations were reduced by both parasympathetic and sympathetic blockade. Thus, a model of associative learning of mild negative emotion in the marmoset has been validated by psychological, neurological, and pharmacological investigation. Future studies will determine the role of the prefrontal cortex in the regulation of these negative emotional responses, to provide insights into the neuropathology of affective disorders.

Serotonin at the level of the amygdala and orbitofrontal cortex modulates distinct aspects of positive emotion in primates

“…All procedures were conducted in accordance with the United Kingdom Animals (Scientific Procedures) Act of 1986, under project licence 80/2225. Following completion of this study, 11 of the marmosets (four out of five controls, three out of four 5,7-DHT amygdala-lesioned animals and all four 5,7-DHT OFC-lesioned animals) were tested on an incongruency discrimination task and the excitotoxic amygdala-lesioned marmosets ( n =3) were tested on the acquisition of a mild aversive Pavlovian procedure, the results of which have been reported, respectively, in Man et al (2010) and Mikheenko et al (2010). A further four marmosets received unilateral 5,7-DHT amygdala lesions to investigate lesion time-course (see Supplementary Materials and methods).…”

Individual differences in behavioral and cardiovascular reactivity to emotive stimuli and their relationship to cognitive flexibility in a primate model of trait anxiety

“…Each subject was transported from the home cage to the apparatus in a clear Perspex box. The carrying box, with the subject, was then fitted into the internal frame of the apparatus; a detailed illustration is given in (Mikheenko et al, 2010). Cardiovascular data were collected by the telemetric receiver (RPC-1, Data Sciences) placed underneath the floor of the internal frame.…”

“…The intra-class correlation coefficient (ICC) was 0.75 [ F (35) = 6.93, p < 0.001] which is within the good range of reliability (Cyr and Francis, 1992). The CS + -related behaviors [typically displayed by marmosets in response to simple Pavlovian conditioning (Mikheenko et al, 2010)] were treated as a single measure of “vigilant scanning” and included attentive visual search of surroundings accompanied by tense postures marked by forward extension of body/head and rearing. The duration of the behavior displayed during the BL and CS periods was scored using a program written in QuickBASIC 4.5.…”

“…Outliers (BP values >400 mmHg or <0 mmHg, or other abnormal spikes) were removed using an algorithm written in Visual Basic, and systolic and diastolic BP events were extracted as local minima and maxima for each heartbeat cycle as described previously (Agustín-Pavón et al, 2012). HR was the more reliable autonomic response to the CS + both within and between animals (Mikheenko et al, 2010) and so together with behavior, was used for the discriminative criterion (Figure 2A). …”

Subcortical projections to the frontal pole in the marmoset monkey

“…We describe the pattern of subcortical afferents to the frontal pole in the marmoset, a New World monkey species that is increasingly being used for investigation of the neural basis of cognition (Dias et al, 1996(Dias et al, , 1997Crofts et al, 2001;Clarke et al, 2005Clarke et al, , 2007Mikheenko et al, 2010;Rygula et al, 2010). The frontal pole, which encompasses cytoarchitectural area 10, remains a relatively unexplored region of the primate brain, despite commanding significant interest because of its expansion and subdivision in primate evolution, and the effects of its lesions in human high-order cognitive processes (Damasio et al, 1994;Semendeferi et al, 2001;Ö ngür et al, 2003).…”