The effect of medial frontal cortex lesions on cardiovascular conditioned emotional responses in the rat

The effect of ventral medial frontal cortex (MFC) lesions on heart rate and blood pressure during conditioned emotional responses (CER) was investigated. Male Sprague-Dawley rats were divided into two groups: MFC-lesioned rats (n = 11) sustained bilateral lesions of the infralimbic and ventral prelimbic regions of the MFC via microinjection of the neurotoxin N-methyl-D-aspartate; Controls (n = 13) received sterile saline. Following a 2-week recovery period, all animals were trained; one of two tones served as the conditioned stimulus (CS) and a 2 mA footshock served as the unconditioned stimulus (US). The CS+ tone was consistently paired with the US, while the CS- tone was randomly paired with the US. Heart rate and blood pressure were recorded during CS+ and CS- presentations before and after administration of the following pharmacological agents: atropine, atenolol, and atropine + atenolol. All animals responded to the CS+ with increased BP compared to baseline; the increase was not significantly different between groups. Controls responded to the CS+ with increased HR, while MFC-lesioned animals displayed a bimodal HR response which was not significantly different from baseline, but was significantly different from Controls. Pharmacological blockade of the HR response revealed coactivation of the sympathetic and parasympathetic nervous systems during the CS+, with a significant decrease (52%) in the sympathetic tachycardia component of the CS+ HR response in MFC-lesioned rats as compared to Controls; the parasympathetic bradycardia component was not altered by MFC lesions. In all cases, CS- responses were smaller than the CS+ responses. Pharmacological analysis revealed that the CS- HR response was mediated by the sympathetic component only, which was also significantly reduced in MFC-lesioned animals as compared to Controls. This significant reduction in the sympathetically mediated HR component of both the reinforced CER (CS+) and the unreinforced CER (CS-) following ventral MFC lesions implies that the MFC is necessary for complete sympathetic activation of cardiovascular responses to both severely and mildly stressful stimuli. The role of the MFC in emotion is also discussed.

[1]  J. van der Meulen,et al.  Social stress induced pressure breathing and consequent blood pressure oscillation. , 1986, Life sciences.

[2]  A. Damasio,et al.  Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli , 1990, Behavioural Brain Research.

[3]  R. M. Beckstead.  An autoradiographic examination of corticocortical and subcortical projections of the mediodorsal‐projection (prefrontal) cortex in the rat , 1979, The Journal of comparative neurology.

[4]  D. Powell,et al.  Lateral hypothalamic lesions: Effects on pavlovian cardiac and eyeblink conditioning in the rabbit , 1981, Brain Research Bulletin.

[5]  Clifford B. Saper,et al.  Reciprocal parabrachial-cortical connections in the rat , 1982, Brain Research.

[6]  J. Stern,et al.  HEART RATE CONDITIONING IN THE RAT. , 1965, Journal of psychosomatic research.

[7]  T. Kaneko,et al.  Direct cortical projections to the parabrachial nucleus in the cat , 1985, The Journal of comparative neurology.

[8]  Joseph E LeDoux,et al.  Destruction of intrinsic neurons in the lateral hypothalamus disrupts the classical conditioning of autonomic but not behavioral emotional responses in the rat , 1986, Brain Research.

[9]  B. Roozendaal,et al.  University of Groningen Differential effect of lesioning of the central amygdala on the bradycardiac and behavioral response of the rat in relation to conditioned social and solitary stress , 2017 .

[10]  C. H. Vanderwolf,et al.  Are emotion and motivation localized in the limbic system and nucleus accumbens? , 1988, Behavioural Brain Research.

[11]  H. A. al Maskati,et al.  Stimulation in prefrontal cortex area inhibits cardiovascular and motor components of the defence reaction in rats. , 1989, Journal of the autonomic nervous system.

[12]  J. Stein,et al.  Functional analysis of hypothalamic control of the cardiovascular responses accompanying emotional behavior. , 1980, Federation proceedings.

[13]  R. Fitzgerald,et al.  Heart-Rate Conditioning in Rats as a Function of Interstimulus Interval , 1971, Psychological reports.

[14]  Y. Hosoya,et al.  Cells of origin of the descending afferents to the lateral hypothalamic area in the rat, studied with the horseradish peroxidase method , 1980, Neuroscience Letters.

[15]  J. Stern,et al.  CLASSICAL HEART RATE CONDITIONING IN THE RAT. , 1963, Journal of psychosomatic research.

[16]  E. Neafsey,et al.  The medial frontal cortex and gastric motility: Microstimulation results and their possible significance for the overall pattern of organization of rat frontal and parietal cortex , 1986, Brain Research.

[17]  K. Spyer,et al.  Interactive responses to stimulation of the amygdaloid central nucleus and baroreceptor afferent activation in the rabbit. , 1989, Journal of the autonomic nervous system.

[18]  W. Nauta.  The problem of the frontal lobe: a reinterpretation. , 1971, Journal of psychiatric research.

[19]  A Sakaguchi,et al.  Subcortical efferent projections of the medial geniculate nucleus mediate emotional responses conditioned to acoustic stimuli , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  R. Rescorla.  Pavlovian conditioning and its proper control procedures. , 1967, Psychological review.

[21]  W. Cannon.  The James-Lange theory of emotions: a critical examination and an alternative theory. By Walter B. Cannon, 1927. , 1927, The American journal of psychology.

[22]  D. Cohen.  Central Processing Time for a Conditioned Response in a Vertebrate Model System , 1982 .

[23]  D. Cohen.  Involvement of the avian amygdalar homologue (archistriatum posterior and mediale) in defensively conditioned heart rate change , 1975, The Journal of comparative neurology.

[24]  E. Neafsey,et al.  The effect of medial frontal cortex lesions on respiration, "freezing," and ultrasonic vocalizations during conditioned emotional responses in rats. , 1991, Cerebral cortex.

[25]  A. Verberne,et al.  Medial prefrontal cortical lesions modulate baroreflex sensitivity in the rat , 1987, Brain Research.

[26]  Bryan Kolb,et al.  Functions of the frontal cortex of the rat: A comparative review , 1984, Brain Research Reviews.

[27]  J. Coyle,et al.  Excitatory amino acid analogues: Neurotoxicity and seizures , 1982, Neuropharmacology.

[28]  Joseph E LeDoux,et al.  Interruption of projections from the medial geniculate body to an archi-neostriatal field disrupts the classical conditioning of emotional responses to acoustic stimuli , 1986, Neuroscience.

[29]  A. Zbrożyna,et al.  Stimulation in prefrontal cortex inhibits conditioned increase in blood pressure and avoidance bar pressing in rats , 1991, Physiology & Behavior.

[30]  F. Isamat,et al.  Galvanic skin responses from stimulation of limbic cortex. , 1961, Journal of neurophysiology.

[31]  G. Aston-Jones,et al.  Diverse afferents converge on the nucleus paragigantocellularis in the rat ventrolateral medulla: Retrograde and anterograde tracing studies , 1989, The Journal of comparative neurology.

[32]  Joseph E LeDoux,et al.  Differential Contribution of Amygdala and Hippocampus to Cued and Contextual Fear Conditioning , 1992 .

[33]  Joseph E LeDoux,et al.  Dissociation of associative and nonassociative concomitants of classical fear conditioning in the freely behaving rat. , 1988, Behavioral neuroscience.

[34]  A. Damasio,et al.  Preserved access and processing of social knowledge in a patient with acquired sociopathy due to ventromedial frontal damage , 1991, Neuropsychologia.

[35]  P. Schmid,et al.  Facilitation of baroreflex-induced bradycardia by stimulation of specific hypothalamic sites in the rat , 1986, Brain Research.

[36]  A. Damasio,et al.  Severe disturbance of higher cognition after bilateral frontal lobe ablation , 1985, Neurology.

[37]  F E Bloom,et al.  The organization of projections from the cortes, amygdala, and hypothalamus to the nucleus of the solitary tract in rat , 1984, The Journal of comparative neurology.

[38]  A. Siegel,et al.  Effects of electrical stimulation of the lateral aspect of the prefrontal cortex upon attack behavior in cats , 1974, Brain Research.

[39]  Renal and hindlimb vascular control during acute emotion in the baboon. , 1979, The American journal of physiology.

[40]  G. Billman,et al.  Mechanisms Mediating the Coronary Vascular Response to Behavioral Stress in the Dog , 1981, Circulation research.

[41]  H. Groenewegen,et al.  Efferent connections of the prelimbic (area 32) and the infralimbic (area 25) cortices: An anterograde tracing study in the cat , 1985, The Journal of comparative neurology.

[42]  G. Martin,et al.  Heart rate and somatomotor activity in rats during signalled escape and yoked classical conditioning , 1980, Physiology & Behavior.

[43]  D. Powell,et al.  Autonomic responses are elicited by electrical stimulation of the medial but not lateral frontal cortex in rabbits , 1985, Behavioural Brain Research.

[44]  J. Lawler,et al.  Alterations in cardiac contractility during classical aversive conditioning in dogs: methodological and theoretical implications. , 1972, Psychophysiology.

[45]  Joseph E LeDoux,et al.  Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  D. Powell,et al.  Cingulate damage attenuates conditioned bradycardia , 1982, Neuroscience Letters.

[47]  G. W. Hoesen,et al.  Central amygdaloid nucleus lesion attenuates exaggerated hemodynamic responses to noise stress in the spontaneously hypertensive rat , 1984, Brain Research.

[48]  A. D. Smith,et al.  A monosynaptic pathway from an identified vasomotor centre in the medial prefrontal cortex to an autonomic area in the thoracic spinal cord , 1993, Neuroscience.

[49]  N. Schneiderman,et al.  The role of amygdaloid central nucleus in the retention of differential pavlovian conditioning of bradycardia in rabbits , 1986, Behavioural Brain Research.

[50]  E. Neafsey,et al.  The topographical organization of neurons in the rat medial frontal, insular and olfactory cortex projecting to the solitary nucleus, olfactory bulb, periaqueductal gray and superior colliculus , 1986, Brain Research.

[51]  C. Saper,et al.  Efferent projections of the infralimbic cortex of the rat , 1991, The Journal of comparative neurology.

[52]  Charles R. Gerfen,et al.  Visceral cortex: A direct connection from prefrontal cortex to the solitary nucleus in rat , 1982, Neuroscience Letters.

[53]  J S Schwaber,et al.  Amygdaloid and basal forebrain direct connections with the nucleus of the solitary tract and the dorsal motor nucleus , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[54]  D. Cohen,et al.  Classical conditioning of cardiovascular responses. , 1984, Annual review of physiology.

[55]  D. Powell,et al.  Cingulate cortex: its role in Pavlovian conditioning. , 1982, Journal of comparative and physiological psychology.

[56]  Michela Gallagher,et al.  Amygdala central nucleus lesions: Effect on heart rate conditioning in the rabbit , 1979, Physiology & Behavior.

[57]  P. M. Duncan.  Effect of septal area damage and base-line activity levels on conditioned heart-rate response in rats. , 1972, Journal of comparative and physiological psychology.

[58]  H. A. al Maskati,et al.  Cardiovascular and motor components of the defence reaction elicited in rats by electrical and chemical stimulation in amygdala. , 1989, Journal of the autonomic nervous system.

[59]  R. Black,et al.  Heart rate conditioning as a function of interstimulus interval in rats , 1967 .