- Log In/Sign Up
- P-ISSN1226-9654
- E-ISSN2733-466X
- KCI
ISSN : 1226-9654
Effects of Electrolytic Lesion of the Prelimbic Area on Context-dependent Fear Discrimination in Rats
Abstract
Recent studies suggest that the medial prefrontal cortex (mPFC) is necessary for the contextual modulation of fear memory. This study investigated whether the prelimbic (PL) subregion of mPFC has influence on the regulation of fear response to the ambiguous CS using contextual information. To verify the hypothetical role of PL, we adopted a context-dependent discriminatory fear conditioning where context dictates CS-US contingency. Rats received 3 pairings of the CS (30-sec, 4-kHz, 75-dB tone) and the US (0.5-sec, 0.5-mA footshock) in context A followed after 1 hour by 10 CS-only trials in context B for 4 days. In the last training session, all rats showed significantly more freezing in context A than in context B. Twenty-four hours after the last training session, PL was lesioned in half of the rats. After eleven days of recovery, we tested the effects of electrolytic lesion of PL on context-dependent discriminatory fear conditioning. PL-lesioned animals showed similar responding to the CS in context A and B, whereas sham-lesioned rats show significantly different responding. This result indicates that the lesion of PL disturbed discriminatory responses to the ambiguous CS when contextual information should be used to resolve the ambiguity of the CS. When all animals were subjected to subsequent training sessions (retraining sessions) for two additional days, PL-lesioned rats acquired context-dependent discriminatory fear memory during the retraining sessions. However, when the rats were tested on the next day, PL-lesioned animals did not show the differential responding to the CS in contextual A and B. This result indicates that PL is necessary for retrieving the learned discriminatory fear memory in the appropriate context. Taken together, these findings suggest that PL might be involved in fear expression under the conditions where the fear responses must be regulated by contexts.
- keywords
- medial prefrontal cortex(mPFC), prelimbic area(PL), context, fear discrimination, freezing, 내측전전두피질, 변연전영역, 맥락, 공포변별학습, 동결반응
Reference
서동오, 이연경, 최준식. (2006) 공포의 생성과 소멸: 파블로프 공포 조건화의 뇌회로를 중심으로. 한국심리학회지: 실험, 18, 1-19.
Antoniadis, E. A., & McDonald, R. J. (2000). Amygdala, hippocampus and discriminative fear conditioning to context. Behavioural brain research, 108(1), 1-19.
Baeg, E. H., Kim, Y. B., Jang, J., Kim, H. T., Mook-Jung, I., & Jung, M. W. (2001). Fast spiking and regular spiking neural correlates of fear conditioning in the medial prefrontal cortex of the rat. Cerebral Cortex, 11(5), 441-451.
Baum, M. (1988). Spontaneous recovery from the effects of flooding (exposure) in animals. Behaviour research and therapy, 26(2), 185-186.
Berretta, S., Pantazopoulos, H., Caldera, M., Pantazopoulos, P., & Pare, D. (2005). Infralimbic cortex activation increases c-Fos expression in intercalated neurons of the amygdala. Neuroscience, 132(4), 943-953.
Bouton, M. E., & King, D. A. (1983). Contextual control of the extinction of conditioned fear: tests for the associative value of the context. Journal of experimental psychology, 9(3), 248-265.
Bouton, M. E., & Swartzentruber, D. (1986). Analysis of the Associative and Occasion-Setting Properties of Contexts Participating in a Pavlovian Discrim. Journal of Experimental Psychology: Animal Behavior Processes, 12(4), 333-350.
Brown, V. J., & Bowman, E. M. (2002). Rodent models of prefrontal cortical function. Trends in neurosciences, 25(7), 340-343.
Burette, F., Jay, T. M., & Laroche, S. (1997). Reversal of LTP in the hippocampal afferent fiber system to the prefrontal cortex in vivo with low-frequency patterns of stimulation that do not produce LTD. Journal of neurophysiology, 78(2), 1155-1160.
Canteras, N. S., & Swanson, L. W. (1992). Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat. The Journal of comparative neurology, 324(2), 180-194.
Carter, C. S., Braver, T. S., Barch, D. M., Botvinick, M. M., Noll, D., & Cohen, J. D. (1998). Anterior cingulate cortex, error detection, and the online monitoring of performance. Science, 280(5364), 747-749.
Carter, C. S., Macdonald, A. M., Botvinick, M., Ross, L. L., Stenger, V. A., Noll, D., et al. (2000). Parsing executive processes: strategic vs. evaluative functions of the anterior cingulate cortex. Proceedings of the National Academy of Sciences of the United States of America, 97(4), 1944-1948.
Cohen, J. D., Dunbar, K., & McClelland, J. L. (1990). On the control of automatic processes: a parallel distributed processing account of the Stroop effect. Psychological review, 97(3), 332-361.
Conde, F., Maire-Lepoivre, E., Audinat, E., & Crepel, F. (1995). Afferent connections of the medial frontal cortex of the rat. II. Cortical and subcortical afferents. The Journal of comparative neurology, 352(4), 567-593.
Corcoran, K. A., Desmond, T. J., Frey, K. A., & Maren, S. (2005). Hippocampal inactivation disrupts the acquisition and contextual encoding of fear extinction. The Journal of Neuroscience, 25(39), 8978-8987.
Corcoran, K. A., & Maren, S. (2001). Hippocampal inactivation disrupts contextual retrieval of fear memory after extinction. The Journal of Neuroscience, 21(5), 1720-1726.
Corcoran, K. A., & Quirk, G. J. (2007a). Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears. The Journal of Neuroscience, 27(4), 840-844.
Corcoran, K. A., & Quirk, G. J. (2007b). Recalling safety: cooperative functions of the ventromedial prefrontal cortex and the hippocampus in extinction. CNS Spectrums, 12(3), 200-206.
Eichenbaum, H., Otto, T., & Cohen, N.J. (1994). Two functional components of the hippocampal. memory system. Behavioral and Brain Sciences, 17(3), 449-517.
Fanselow, M. S. (2000). Contextual fear, gestalt memories, and the hippocampus. Behavioural brain research, 110(1-2), 73-81.
Fanselow, M. S., & Helmstetter, F. J. (1988). Conditional analgesia, defensive freezing, and benzodiazepines. Behavioral neuroscience, 102(2), 233-243.
Farinelli, M., Deschaux, O., Hugues, S., Thevenet, A., & Garcia, R. (2006). Hippocampal train stimulation modulates recall of fear extinction independently of prefrontal cortex synaptic plasticity and lesions. Learning & memory, 13(3), 329-334.
Fendt, M., & Fanselow, M. S. (1999). The neuroanatomical and neurochemical basis of conditioned fear. Neuroscience Biobehaviral Reviews, 23(5), 743-760.
Frankland, P. W., Cestari, V., Filipkowski, R. K., McDonald, R. J., & Silva, A. J. (1998). The dorsal hippocampus is essential for context discrimination but not for contextual conditioning. Behavioral neuroscience, 112(4), 863-874.
Gonzalez, L. E., Quinonez, B., Rangel, A., Pino, S., & Hernandez, L. (2004). Tonic and phasic alteration in amygdala 5-HT, glutamate and GABA transmission after prefrontal cortex damage in rats. Brain research, 1005(1-2), 154-163.
Haddon, J. E., & Killcross, A. S. (2005). Medial prefrontal cortex lesions abolish contextual control of competing responses. Journal of the Experimental Analysis of Behavior, 84(3), 485-504.
Haddon, J. E., & Killcross, S. (2006). Prefrontal cortex lesions disrupt the contextual control of response conflict. The Journal of Neuroscience, 26(11), 2933-2940.
Hugues, S., & Garcia, R. (2007). Reorganization of learning-associated prefrontal synaptic plasticity between the recall of recent and remote fear extinction memory. Learning & memory, 14(8), 520-524.
Ishikawa, A., & Nakamura, S. (2003). Convergence and interaction of hippocampal and amygdalar projections within the prefrontal cortex in the rat. The Journal of Neuroscience, 23(31), 9987-9995.
Jay, T. M., Glowinski, J., & Thierry, A. M. (1989). Selectivity of the hippocampal projection to the prelimbic area of the prefrontal cortex in the rat. Brain research, 505(2), 337-340.
Jay, T. M., & Witter, M. P. (1991). Distribution of hippocampal CA1 and subicular efferents in the prefrontal cortex of the rat studied by means of anterograde transport of Phaseolus vulgaris-leucoagglutinin. The Journal of Comparative Neurology, 313(4), 574-586.
Ji, J., & Maren, S. (2005). Electrolytic lesions of the dorsal hippocampus disrupt renewal of conditional fear after extinction. Learning & memory, 12(3), 270-276.
Kalisch, R., Korenfeld, E., Stephan, K. E., Weiskopf, N., Seymour, B., & Dolan, R. J. (2006). Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network. The Journal of Neuroscience, 26(37), 9503-9511.
Kerns, J. G., Cohen, J. D., MacDonald, A. W., 3rd, Johnson, M. K., Stenger, V. A., Aizenstein, H., et al. (2005). Decreased conflict- and error-related activity in the anterior cingulate cortex in subjects with schizophrenia. The American Journal of Psychiatry, 162(10), 1833-1839.
Kolb, B. (1990). Prefrontal cortex. In B. Kolb, Tees, R. (Ed.), The Cerebral Cortex. London: MIT.
Laroche, S., Davis, S., & Jay, T. M. (2000). Plasticity at hippocampal to prefrontal cortex synapses: dual roles in working memory and consolidation. Hippocampus, 10(4), 438-446.
Laroche, S., Jay, T. M., & Thierry, A. M. (1990). Long-term potentiation in the prefrontal cortex following stimulation of the hippocampal CA1/subicular region. Neurosci Lett, 114(2), 184-190.
Lavond, D. G., Kim, J. J., & Thompson, R. F. (1993). Mammalian brain substrates of aversive classical conditioning. Annual Review of Psychology, 44, 317-342.
Lebron, K., Milad, M. R., & Quirk, G. J. (2004). Delayed recall of fear extinction in rats with lesions of ventral medial prefrontal cortex. Learning & Memory, 11(5), 544-548.
LeDoux, J. E. (1996). Emotional networks and motor control: a fearful view. Progress in Brain Research, 107, 437-446.
LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155-184.
MacDonald, A. W., 3rd, Cohen, J. D., Stenger, V. A., & Carter, C. S. (2000). Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science, 288(5472), 1835-1838.
Maren, S., & Fanselow, M. S. (1995). Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo. The Journal of Neuroscience, 15(11), 7548-7564.
Maren, S., & Fanselow, M. S. (1996). The amygdala and fear conditioning: has the nut been cracked? Neuron, 16(2), 237-240.
Maren, S., & Hobin, J. A. (2007). Hippocampal regulation of context-dependent neuronal activity in the lateral amygdala. Learning & Memory, 14(4), 318-324.
Marquis, J. P., Killcross, S., & Haddon, J. E. (2007). Inactivation of the prelimbic, but not infralimbic, prefrontal cortex impairs the contextual control of response conflict in rats. European Journal of Neuroscience, 25(2), 559-566.
Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T., Rammes, G., Cascio, M. G., et al. (2002). The endogenous cannabinoid system controls extinction of aversive memories. Nature, 418(6897), 530-534.
McDonald, A. J., Mascagni, F., & Guo, L. (1996). Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience, 71(1), 55-75.
Milad, M. R., & Quirk, G. J. (2002). Neurons in medial prefrontal cortex signal memory for fear extinction. Nature, 420(6911), 70-74.
Milad, M. R., Wright, C. I., Orr, S. P., Pitman, R. K., Quirk, G. J., & Rauch, S. L. (2007). Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biological Psychiatry, 62(5), 446-454.
Morgan, M. A., & LeDoux, J. E. (1995). Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behavioral Neuroscience, 109(4), 681-688.
Morgan, M. A., Romanski, L. M., & LeDoux, J. E. (1993). Extinction of emotional learning: contribution of medial prefrontal cortex. Neuroscience Letters, 163(1), 109-113.
Morgan, M. A., Schulkin, J., & LeDoux, J. E. (2003). Ventral medial prefrontal cortex and emotional perseveration: the memory for prior extinction training. Behavioural Brain Research, 146(1-2), 121-130.
Pavlov, I. (1927). Conditioned reflex. London: Oxford UP.
Phelps, E. A., Delgado, M. R., Nearing, K. I., & LeDoux, J. E. (2004). Extinction learning in humans: role of the amygdala and vmPFC. Neuron, 43(6), 897-905.
Phillips, R. G., & LeDoux, J. E. (1992). Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behavioral Neuroscience, 106(2), 274-285.
Quirk, G. J., & Beer, J. S. (2006). Prefrontal involvement in the regulation of emotion: convergence of rat and human studies. Current Opinion in Neurobiology, 16(6), 723-727.
Quirk, G. J., Russo, G. K., Barron, J. L., & Lebron, K. (2000). The role of ventromedial prefrontal cortex in the recovery of extinguished fear. The Journal of Neuroscience, 20(16), 6225-6231.
Ragozzino, M. E., Detrick, S., & Kesner, R. P. (1999). Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning. The Journal of Neuroscience, 19(11), 4585-4594.
Ragozzino, M. E., Wilcox, C., Raso, M., & Kesner, R. P. (1999). Involvement of rodent prefrontal cortex subregions in strategy switching. Behavioral Neuroscience, 113(1), 32-41.
Rescorla, R. A., & Heth, C. D. (1975). Reinstatement of fear to an extinguished conditioned stimulus. Journal of Experimental Psychology: Animal Behavior Processes, 1(1), 88-96.
Rougier, N. P., Noelle, D. C., Braver, T. S., Cohen, J. D., & O'Reilly, R. C. (2005). Prefrontal cortex and flexible cognitive control: rules without symbols. Proceedings of the National Academy of Sciences of the United States of America, 102(20), 7338-7343.
Santini, E., Ge, H., Ren, K., Pena de Ortiz, S., & Quirk, G. J. (2004). Consolidation of fear extinction requires protein synthesis in the medial prefrontal cortex. The Journal of Neuroscience, 24(25), 5704-5710.
Sierra-Mercado, D., Jr., Corcoran, K. A., Lebron-Milad, K., & Quirk, G. J. (2006). Inactivation of the ventromedial prefrontal cortex reduces expression of conditioned fear and impairs subsequent recall of extinction. European Journal of Neuroscience, 24(6), 1751-1758.
Sotres-Bayon, F., Cain, C. K., & LeDoux, J. E. (2006). Brain mechanisms of fear extinction: historical perspectives on the contribution of prefrontal cortex. Biological Psychiatry, 60(4), 329-336.
Takita, M., Izaki, Y., Jay, T. M., Kaneko, H., & Suzuki, S. S. (1999). Induction of stable long-term depression in vivo in the hippocampal-prefrontal cortex pathway. European Journal of Neuroscience, 11(11), 4145-4148.
Thierry, A. M., Gioanni, Y., Degenetais, E., & Glowinski, J. (2000). Hippocampo-prefrontal cortex pathway: anatomical and electrophysiological characteristics. Hippocampus, 10(4), 411-419.
Uylings, H. B., Groenewegen, H. J., & Kolb, B. (2003). Do rats have a prefrontal cortex? Behav Brain Research, 146(1-2), 3-17.
Vertes, R. P. (2004). Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse, 51(1), 32-58.
Vidal-Gonzalez, I., Vidal-Gonzalez, B., Rauch, S. L., & Quirk, G. J. (2006). Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learning & Memory, 13(6), 728-733.
- Downloaded
- Viewed
- 0KCI Citations
- 0WOS Citations