Abstract
Ambulatory locomotion in the rodent is robustly activated by unilateral infusions into the basal forebrain of type A gamma-aminobutyric acid receptor antagonists, such as bicuculline and picrotoxin. The present study was carried out to better localize the neuroanatomical substrate(s) underlying this effect. To accomplish this, differences in total locomotion accumulated during a 20-min test period following bicuculline versus saline infusions in male Sprague–Dawley rats were calculated, rank ordered and mapped on a diagram of basal forebrain transposed from immunoprocessed sections. The most robust locomotor activation was elicited by bicuculline infusions clustered in rostral parts of the preoptic area. Unilateral infusions of bicuculline into the ventral pallidum produced an unanticipatedly diminutive activation of locomotion, which led us to evaluate bilateral ventral pallidal infusions, and these also produced only a small activation of locomotion, and, interestingly, a non-significant trend toward suppression of rearing. Subjects with bicuculline infused bilaterally into the ventral pallidum also exhibited persistent bouts of abnormal movements. Bicuculline infused unilaterally into other forebrain structures, including the bed nucleus of stria terminalis, caudate-putamen, globus pallidus, sublenticular extended amygdala and sublenticular substantia innominata, did not produce significant locomotor activation. Our data identify the rostral preoptic area as the main substrate for the locomotor-activating effects of basal forebrain bicuculline infusions. In contrast, slight activation of locomotion and no effect on rearing accompanied unilateral and bilateral ventral pallidal infusions. Implications of these findings for forebrain processing of reward are discussed.
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Alheid GF, Heimer L (1988) New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 27:1–39
Alheid GF, Beltramino C, Braun A, Miselis RR, François C, de Olmos JS (1994) Transition areas of the striatopallidal system and extended amygdala in the rat and primate: observations from histochemistry and experiments with mono- and trans-synaptic tracer. In: Percheron G, McKenzie JS, Féger J (eds) The Basal Ganglia IV, vol 41, new ideas and data on structure and function. Plenum Press, New York, pp 95–107
Alheid GF, de Olmos JS, Beltramino CA (1995) Amygdala and extended amygdala. In: Paxinos G (ed) The rat nervous system, 2nd edn. Academic Press, San Diego, pp 495–578
Alheid GF, Beltramino CA, De Olmos JS, Forbes MS, Swanson DJ, Heimer L (1998) The neuronal organization of the supracapsular part of the stria terminalis in the rat: the dorsal component of the extended amygdala. Neuroscience 84:967–996
Alheid GF, Shammah-Lagnado SJ, Beltramino CA (1999) The interstitial nucleus of the posterior limb of the anterior commissure: a novel layer of the central division of extended amygdala. Ann N Y Acad Sci 877:645–654
Austin MC, Kalivas PW (1989) Blockade of enkephalinergic and GABAergic mediated locomotion in the nucleus accumbens by muscimol in the ventral pallidum. Jpn J Pharmacol 50:487–490
Austin MC, Kalivas PW (1990) Enkephalinergic and GABAergic modulation of motor activity in the ventral pallidum. J Pharmacol Exp Ther 252:1370–1377
Austin MC, Kalivas PW (1991) Dopaminergic involvement in locomotion elicited from the ventral pallidum/substantia innominata. Brain Res 542:123–131
Berridge KC, Robinson TE (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev 28:309–369
Blaha CD, Coury A, Fibiger HC, Phillips AG (1990) Effects of neurotensin on dopamine release and metabolism in the rat striatum and nucleus accumbens: cross-validation using in vivo voltammetry and microdialysis. Neuroscience 34:699–705
Breese GR, Howard JL, Leahy JP (1971) Effect of 6-hydroxydopamine on electrical self stimulation of the brain. Br J Pharmacol 43:255–257
Bushnik T, Bielajew C, Konkle AT (2000) The substrate for brain-stimulation reward in the lateral preoptic area. I. Anatomical mapping of its boundaries. Brain Res 881:103–111
Cador M, Taylor JR, Robbins TW (1991) Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens. Psychopharmacology 104:377–385
Celio MR, Heizmann CW (1981) Calcium-binding protein parvalbumin as a neuronal marker. Nature 293:300–302
Chapman MA, Zahm DS (1996) Altered Fos-like immunoreactivity in terminal regions of the mesotelencephalic dopamine system is associated with reappearance of tyrosine hydroxylase immunoreactivity at the sites of focal 6-hydroxydopamine lesions in the nucleus accumbens. Brain Res 736:270–279
Chen JC, Liang KW, Huang YK, Liang CS, Chiang YC (2001) Significance of glutamate and dopamine neurons in the ventral pallidum in the expression of behavioral sensitization to amphetamine. Life Sci 68:973–983
Cowan RL, Wilson CJ, Emson PC, Heizmann CW (1990) Parvalbumin containing GABAergic interneurons in the rat neostriatum. J Comp Neurol 302:197–205
de Olmos JS, Ingram WR (1972) The projection field of the stria terminalis in the rat brain. An experimental study. J Comp Neurol 146:303–334
Dray A (1975) Comparison of bicuculline methochloride with bicuculline and picrotoxin as antagonists of amino acid and monamine depression of neurones in the rat brainstem. Neuropharmacol 14:887–891
Elliott PJ, Nemeroff CB (1986) Repeated neurotensin administration in the ventral tegmental area: effects on baseline and D-amphetamine-induced locomotor activity. Neurosci Lett 68:239–244
Fibiger HC, Carter DA, Phillips AG (1976) Decreased intracranial self-stimulation after neuroleptics or 6-hydroxydopamine: evidence for mediation by motor deficits rather than by reduced reward. Psychopharmacology 47:21–27
Fibiger HC, LePiane FG, Jakubovic A, Phillips AG (1987) The role of dopamine in intracranial self-stimulation of the ventral tegmental area. J Neurosci 7:3888–3896
Floresco SB, West AR, Ash B, Moore H, Grace AA (2003) Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat Neurosci 6:968–973
Gallistel CR, Gomita Y, Yadin E, Campbell KA (1985) Forebrain origins and terminations of the medial forebrain bundle metabolically activated by rewarding stimulation or by reward-blocking doses of pimozide. J Neurosci 5:1246–1261
Geisler S, Zahm DS (2005) Afferents of the ventral tegmental area in the rat—anatomical substratum for integrative functions. J Comp Neurol 490:270–294
Geisler S, Zahm DS (2006a) Neurotensinergic afferents of the ventral tegmental area in the rat: [1] re-examination of the origins and [2] responses to acute psychostimulant drug administration. Eur J Neurosci 24:116–134
Geisler S, Zahm DS (2006b) On the retention of neurotensin in the ventral tegmental area (VTA) despite destruction of the main neurotensinergic afferents of the VTA–implications for the organization of forebrain projections to the VTA. Brain Res 1087:87–104
Geisler S, Derst C, Veh RW, Zahm DS (2007) Glutamatergic afferents of the ventral tegmental area in the rat. J Neurosci 27:5730–5743
Gerfen CR, Baimbridge KG, Miller JJ (1985) The neostriatal mosaic: compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey. Proc Natl Acat Sci USA 82:8780–8784
Glimcher PW, Margolin DH, Giovino AA, Hoebel BG (1984) Neurotensin: a new ‘reward peptide’. Brain Res 291:119–124
Glimcher PW, Giovino AA, Hoebel BG (1987) Neurotensin self-injection in the ventral tegmental area. Brain Res 403:147–150
Gong W, Neill DB, Lynn M, Justice JB Jr (1999) Dopamine D1/D2 agonists injected into nucleus accumbens and ventral pallidum differentially affect locomotor activity depending on site. Neuroscience 93:1349–1358
Groenewegen HJ, Berendse HW, Haber SN (1993) Organization of the output of the ventral striatopallidal system in the rat: ventral pallidal efferents. Neuroscience 57:113–142
Heidbreder C, Gewiss M, De Mot B, Mertens I, De Witte P (1992) Balance of glutamate and dopamine in the nucleus accumbens modulates self-stimulation behavior after injection of cholecystokinin and neurotensin in the rat brain. Peptides 13:441–449
Heimer L (1972) The olfactory connections of the diencephalon in the rat. An experimental light- and electron-microscopic study with special emphasis on the problem of terminal degeneration. Brain Behav Evol 6:484–523
Heimer L, Alheid GF (1991) Piecing together the puzzle of basal forebrain anatomy. Adv Exp Med Biol 295:1–42
Heimer L, Wilson RD (1975) The subcortical projections of allocortex: similarities in the neuroal associations of the hippocampus, the piriform cortex and the neocortex. In: Santini M (ed) Golgi centennial symposium proceedings. Raven Press, New York, pp 173–193
Heimer L, de Olmos J, Alheid GF, Zaborszky L (1991) “Perestroika” in the basal forebrain: opening the border between neurology and psychiatry. Prog Brain Res 87:109–165
Heimer L, Harlan RE, Alheid GF, Garcia M, de Olmos J (1997) Substantia innominata: a notion which impedes clinical-anatomical correlations in neuropsychiatric disorders. Neuroscience 76:957–1006
Heimer L, de Olmos J, Alheid GF, Pearson J, Sakamoto M, Marksteiner J, Switzer RC III (1999) The human basal forebrain, part 2. In: Bloom FE, Bjorklund A, Hokfelt T (eds) Handbook of chemical neuroanatomy, vol 15. Elsevier, Amsterdam, pp 57–226
Holstege G (1991) Descending motor pathways and the spinal motor system: limbic and non-limbic components. Prog Brain Res 87:307–421
Holstege G (1992) The emotional motor system. Eur J Morphol 30:67–79
Holstege G, Mouton LG, Gerrits MN (2004) Emotional motor system. In: Paxinos G, Mai JK (eds) The human nervous system. Elsevier, Amsterdam, pp 1306–1324
Hotsenpiller G, Giorgetti M, Wolf ME (2001) Alterations in behaviour and glutamate transmission following presentation of stimuli previously associated with cocaine exposure. Eur J Neurosci 14:1843–1855
Hubert GW, Manvich DF, Kuhar MJ (2010) Cocaine and amphetamine-regulated transcript-containing neurons in the nucleus accumbens project to the ventral pallidum in the rat and may inhibit cocaine-induced locomotion. Neuroscience 165:179–187
Itoh Z, Akiva K, Nomura S, Mizuno N, Hakamura Y, Sugimoto T (1979) Application of a coupled oxidation reaction to electron microscopic demonstraion of horseradish peroxidase: cobalt-glucose oxidase method. Brain Res 175:341–347
Jhou TC, Geisler S, Marinelli M, Degarmo BA, Zahm DS (2009) The mesopontine rostromedial tegmental nucleus: a structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta. J Comp Neurol 513:566–596
Johnson PI, Napier TC (2000) Ventral pallidal injections of a mu antagonist block the development of behavioral sensitization to systemic morphine. Synapse 38:61–70
Johnson K, Churchill L, Klitenick MA, Hooks MS, Kalivas PW (1996) Involvement of the ventral tegmental area in locomotion elicited from the nucleus accumbens or ventral pallidum. J Pharmacol Exp Ther 277:1122–1131
June HL, Foster KL, McKay PF, Seyoum R, Woods JE, Harvey SC, Eiler WJ, Grey C, Carroll MR, McCane S, Jones CM, Yin W, Mason D, Cummings R, Garcia M, Ma C, Sarma PV, Cook JM, Skolnick P (2003) The reinforcing properties of alcohol are mediated by GABA(A1) receptors in the ventral pallidum. Neuropsychopharmacology 28:2124–2137
Kalivas PW, Duffy P (1990) Effect of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens. Synapse 5:48–58
Kalivas PW, Taylor S (1985) Behavioral and neurochemical effect of daily injection with neurotensin into the ventral tegmental area. Brain Res 358:70–76
Kalivas PW, Nemeroff CB, Prange AJ Jr (1982) Neuroanatomical site specific modulation of spontaneous motor activity by neurotensin. Eur J Pharmacol 78:471–474
Kalivas PW, Burgess SK, Nemeroff CB, Prange AJ Jr (1983) Behavioral and neurochemical effects of neurotensin microinjection into the ventral tegmental area of the rat. Neuroscience 8:495–505
Kalivas PW, Klitenick MA, Hagler H, Austin MC (1991) GABAergic and enkephalinergic regulation of locomotion in the ventral pallidum: involvement of the mesolimbic dopamine system. In: Napier TC, Kaliavs PW, Hanin I (eds) The basal forebrain. Anatomy to function. Plenum Press, NY (Adv Exp Med Biol 295), pp 315–326
Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522
Kemppainen H, Raivio N, Kiianmaa K (2012) Role for ventral pallidal GABAergic mechanisms in the regulation of ethanol self-administration. Psychopharmacology 223:211–221
Krishek BJ, Moss SJ, Smart TG (1996) A functional comparison of the antagonists bicuculline and picrotoxin at recominant GABAA receptors. Neuropharmacol 35:1289–1298
Laitinen K, Crawley JN, Mefford IN, De Witte P (1990) Neurotensin and cholecystokinin microinjected into the ventral tegmental area modulate microdialysate concentrations of dopamine and metabolites in the posterior nucleus accumbens. Brain Res 523:342–346
Lavezzi HN, Zahm DS (2011) The mesopontine rostromedial tegmental nucleus: an integrative modulator of the reward system. Basal Ganglia 1:191–200
Lodge DJ, Grace AA (2006) The hippocampus modulates dopamine neuron responsivity by regulating the intensity of phasic neuron activation. Neuropsychopharmacology 31:1356–1361
Mary Christopher S, Butter CM (1968) Consummatory behaviors and locomotor exploration evoked from self-stimulation sites in rats. J Comp Physiol Psychol 66:335–339
Mogenson GJ, Nielsen MA (1983) Evidence that an accumbens to subpallidal GABAergic projection contributes to locomotor activity. Brain Res Bull 11:309–314
Mogenson GJ, Yang CR (1991) The contribution of basal forebrain to limbic-motor integration and the mediation of motivation to action. In: Napier TC, Kaliavs PW, Hanin I (eds) The basal forebrain. Anatomy to function. Plenum Press, NY (Adv Exp Med Biol 295), pp 267–290
Mogenson GJ, Swanson LW, Wu M (1983) Neural projections from nucleus accumbens to globus pallidus, substantia innominata, and lateral preoptic-lateral hypothalamic area: an anatomical and electrophysiological investigation in the rat. J Neurosci 3:189–202
Mogenson GJ, Swanson LW, Wu M (1985) Evidence that projections from substantia innominata to zona incerta and mesencephalic locomotor region contribute to locomotor activity. Brain Res 334:65–76
Mogenson GJ, Brudzynski SM, Wu M, Yang CR, Yim CY (1993) From motivation to action: a review of dopaminergic regulation of limbic-nucleus accumbens-ventral pallidum-pedunculopontine nucleus circuitries involved in limbic-motor integration. In: Kalivas PW, Barnes CD (eds) Limbic Motor Circuits and Neuropsychiatry. CRC Press, Boca Raton, FL (Adv Exp Med Biol 295), pp 193–236
Newman SW (1999) The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network. In: McGinty J (ed) Advancing from the ventral striatum to the extended amydala. Implications for neuropsychiatry and drug abuse. Ann NY Acad Sci 877:242–257
Phillipson OT (1979) Afferent projections to the ventral tegmental area of Tsai and interfascicular nucleus: a horseradish peroxidase study in the rat. J Comp Neurol 187:117–143
Reynolds SM, Geisler S, Berod A, Zahm DS (2006) Neurotensin antagonist acutely and robustly attenuates locomotion that accompanies stimulation of a neurotensin-containing pathway from rostrobasal forebrain to the ventral tegmental area. Eur J Neurosci 24:188–196
Rivest R, Jolicoeur FB, Marsden CA (1991) Neurotensin causes a greater increase in the metabolism of dopamine in the accumbens than in the striatum in vivo. Neuropharmacology 30:25–33
Roberts WW, Carey RJ (1965) Rewarding effect of performance of gnawing aroused by hypothalamic stimulation in the rat. J Comp Physiol Psychol 59:317–324
Rodrigo J, Springall DR, Uttenthal O, Bentura ML, Abadia-Molina F, Riveros-Moreno V, Martínez-Murillo R, Polak JM, Moncada S (1994) Localization of nitric oxide synthase in the adult rat brain. Philos Trans R Soc Lond B Biol Sci 345:175–221
Rompre PP (1995) Psychostimulant-like effect of central microinjection of neurotensin on brain stimulation reward. Peptides 16:1417–1420
Rompre PP, Gratton A (1993) Mesencephalic microinjections of neurotensin-(1–13) and its C-terminal fragment, neurotensin-(8–13), potentiate brain stimulation reward. Brain Res 616:154–162
Rompre PP, Bauco P, Gratton A (1992) Facilitation of brain stimulation reward by mesencephalic injections of neurotensin-(1–13). Eur J Pharmacol 211:295–303
Root DH, Ma S, Barker DJ, Megehee L, Striano BM, Ralston CM, Fabbricatore AT, West MO (2013) Differential roles of ventral pallidum subregions during cocaine self-administration behaviors. J Comp Neurol 521:558–588
Sakamoto M, Pearson J, Shinoda K, Alheid GF, de Olmos JS, Heimer L (1999) The human basal forebrain, part 1. An overview. In: Bloom FE, Bjorklund A, Hokfelt T (eds) Handbook of chemical neuroanatomy, vol 15. Elsevier, Amsterdam, pp 1–55
Sesack SR, Grace AA (2010) Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacol 35:27–47
Shreve PE, Uretsky NJ (1988) Effect of GABAergic transmission in the subpallidal region on the hypermotility response to the administration of excitatory amino acids and picrotoxin into the nucleus accumbens. Neuropharmacology 27:1271–1277
Shreve PE, Uretsky NJ (1989) AMPA, kainic acid, and N-methyl-d-aspartic acid stimulate locomotor activity after injection into the substantia innominata/lateral preoptic area. Pharmacol Biochem Behav 34:101–106
Shreve PE, Uretsky NJ (1991) GABA and glutamate interact in the substantia innominata/lateral preoptic area to modulate locomotor activity. Pharmacol Biochem Behav 38:385–388
Simmonds MA (1982) Classification of GABA antagonists with regard to site of action and potency in slices of rat cuneate nucleus. Eur J Pharmacol 347–358
Sotty F, Souliere F, Brun P, Chouvet G, Steinberg R, Soubrie P, Renaud B, Suaud-Chagny MF (1998) Differential effects of neurotensin on dopamine release in the caudal and rostral nucleus accumbens: a combined in vivo electrochemical and electrophysiological study. Neuroscience 85:1173–1182
Sotty F, Brun P, Leonetti M, Steinberg R, Soubrie P, Renaud B, Suaud-Chagny MF (2000) Comparative effects of neurotensin, neurotensin(8–13) and [D-Tyr(11)]neurotensin applied into the ventral tegmental area on extracellular dopamine in the rat prefrontal cortex and nucleus accumbens. Neuroscience 98:485–492
Steinberg R, Brun P, Fournier M, Souilhac J, Rodier D, Mons G, Terranova JP, Le Fur G, Soubrie P (1994) SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission. Neuroscience 59:921–929
Swerdlow NR, Koob GF (1984) The neural substrates of apomorphine-stimulated locomotor activity following denervation of the nucleus accumbens. Life Sci 35:2537–2544
Switzer RC 3rd, Hill J, Heimer L (1982) The globus pallidus and its rostroventral extension into the olfactory tubercle of the rat: a cyto- and chemoarchitectural study. Neuroscience 7:1891–1904
Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology 84:405–412
Taylor JR, Robbins TW (1986) 6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbens d-amphetamine. Psychopharmacology 90:390–397
Tindell AJ, Berridge KC, Aldridge JW (2004) Ventral pallidal representation of pavlovian cues and reward: population and rate codes. J Neurosci 24:1058–1069
Tindell AJ, Berridge KC, Zhang J, Pecina S, Aldridge JW (2005) Ventral pallidal neurons code incentive motivation: amplification by mesolimbic sensitization and amphetamine. Eur J Neurosci 22:2617–2634
Tindell AJ, Smith KS, Pecina S, Berridge KC, Aldridge JW (2006) Ventral pallidum firing codes hedonic reward: when a bad taste turns good. J Neurophysiol 96:2399–2409
Watabe-Uchida M, Zhu L, Ogawa SK, Vamanrao A, Uchida N (2012) Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron 74:858–873
Willins DL, Wallace LJ, Miller DD, Uretsky NJ (1992) Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonists in the nucleus accumbens and ventral pallidum decrease the hypermotility response to psychostimulant drugs. J Pharmacol Exp Ther 260:1145–1151
Zaborszky L, Cullinan WE, Braun A (1991) Afferents to basal forebrain cholinergic neurons: an update. In: Napier TC, Kalivas PW, Hanin I (eds) The basal forebrain. Anatomy to function. Plenum Press, New York, pp 43–100
Zahm DS (1989) The ventral striatopallidal parts of the basal ganglia in the rat–II. Compartmentation of ventral pallidal efferents. Neuroscience 30:33–50
Zahm DS (1999) Functional-anatomical implications of the nucleus accumbens core and shell subterritories. Ann N Y Acad Sci 877:113–128
Zahm DS, Grosu S, Williams EA, Qin S, Berod A (2001) Neurons of origin of the neurotensinergic plexus enmeshing the ventral tegmental area in rat: retrograde labeling and in situ hybridization combined. Neuroscience 104:841–851
Zahm DS, Grosu S, Irving JC, Williams EA (2003) Discrimination of striatopallidum and extended amygdala in the rat: a role for parvalbumin immunoreactive neurons? Brain Res 978:141–154
Zahm DS, Cheng AY, Lee TJ, Ghobadi CW, Schwartz ZM, Geisler S, Parsely KP, Gruber C, Veh RW (2011) Inputs to the midbrain dopaminergic complex in the rat, with emphasis on extended amygdala-recipient sectors. J Comp Neurol 519:3159–3188
Zahm DS, Schwartz ZM, Lavezzi HN, Parsley KP (2012) Locomotion elicited by infusion of bicuculline into the lateral preoptic area persists during blockade of dopamine receptors. Soc Neurosci Abstr 183:13
Zahm DS, Parsley KP, Schwartz ZM, Cheng AY (2013) On lateral septum-like characteristics of outputs from the accumbal hedonic ‘hotspot’ of Pecina and Berridge with commentary on the transitional nature of basal forebrain ‘boundaries’. J Comp Neurol 521:50–68
Zukin SR, Young AB, Snyder SH (1974) Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system. Proc Natl Acad Sci USA 71:4802
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This work was supported by USPHS NIH grant NS-23805.
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Zahm, D.S., Schwartz, Z.M., Lavezzi, H.N. et al. Comparison of the locomotor-activating effects of bicuculline infusions into the preoptic area and ventral pallidum. Brain Struct Funct 219, 511–526 (2014). https://doi.org/10.1007/s00429-013-0514-x
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DOI: https://doi.org/10.1007/s00429-013-0514-x