Blocking NMDA-receptors in the pigeon’s “prefrontal” caudal nidopallium impairs appetitive extinction learning in a sign-tracking paradigm

Abstract

Extinction learning provides the ability to flexibly adapt to new contingencies by learning to inhibit previously acquired associations in a context-dependent manner. The neural networks underlying extinction learning were mostly studied in rodents using fear extinction paradigms. To uncover invariant properties of the neural basis of extinction learning, we employ pigeons as a model system. Since the prefrontal cortex (PFC) of mammals is a key structure for extinction learning, we assessed the role of N-methyl-D-aspartate receptors (NMDARs) in the nidopallium caudolaterale (NCL), the avian functional equivalent of mammalian PFC. Since NMDARs in PFC have been shown to be relevant for extinction learning, we locally antagonized NMDARs through 2-Amino-5-phosphonovalerianacid (APV) during extinction learning in a within-subject sign-tracking ABA-renewal paradigm. APV-injection slowed down extinction learning and in addition also caused a disinhibition of responding to a continuously reinforced control stimulus. In subsequent retrieval sessions, spontaneous recovery was increased while ABA renewal was unaffected. The effect of APV resembles that observed in studies of fear extinction with rodents, suggesting common neural substrates of extinction under both appetitive and aversive conditions and highlighting the similarity of mammalian PFC and the avian caudal nidopallium despite 300 million years of independent evolution.

Cortical inter‐hemispheric circuits for multimodal vocal learning in songbirds

“…In addition, NMDAR‐mediated currents within this region are required for auditory and visual imprinting, another type of developmentally regulated multimodal learning (Bock & Braun, ; Bock, Schnabel, & Braun, ; Braun et al, ; Van Kampen & Bolhuis, ). Pigeon caudal nidopallium also receives visual, auditory, and somatosensory inputs, and blocking N‐methyl‐D‐aspartate (NMDA) receptors in this region interferes with a pigeon's ability to learn new tasks and remember previously learned behaviors (Diekamp, Kalt, & Gunturkun, ; Gunturkun, ; Herold et al, ; Kroner & Gunturkun, ; Lengersdorf, Marks, Uengoer, Stuttgen, & Gunturkun, ; Shanahan et al, ). In zebra finch, NMDA receptors are known to mediate over 90% of synaptic transmission from the thalamus (dorsolateral anterior thalamic nucleus, DLM) to LMAN and from LMAN‐CORE to vocal motor cortex (RA) (Bottjer, ; Stark & Perkel, ; Wang & Hessler, ; White, Livingston, & Mooney, ).…”

Relative Brain Size and Its Relation with the Associative Pallium in Birds

“…The nidopallium, in particular its caudolateral part, the NCL, is the closest avian equivalent of the mammalian pre-frontal cortex. Several lines of evidence, using different approaches and techniques (connectome [Shanahan et al, 2013], single-unit recording [Rose and Colombo, 2005;Veit and Nieder, 2013;Lengersdorf et al, 2015], receptor architecture [Rose et al, 2010;Herold et al, 2011], temporary inactivation [Helduser and Güntürkün, 2012] and lesions [Mogensen and Divac, 1993]) point to the importance of the NCL in avian executive control. Comparative work also suggests that the nidopallium is the brain area most closely correlated with avian tool use [Lefebvre et al, 2002], while the other part of the associative pallium, i.e.…”

A comparative analysis of the dopaminergic innervation of the executive caudal nidopallium in pigeon, chicken, zebra finch, and carrion crow

“…On a functional level, the PFC and NCL have been implicated in a range of behaviors that recruit self‐control, working memory and cognitive flexibility—the core concepts of executive functioning (Diamond, ; Fuster, ; Güntürkün, , ; Nieder, ). Lesion‐ and pharmacological blockade studies demonstrate that ablation of these executive structure interferes with performance on spatial and nonspatial working memory tasks (pigeon: Diekamp, Diekamp, Gagliardo, & Güntürkün, ; Gagliardo, Bonadonna, & Divac, ; Güntürkün, ; Lissek & Güntürkün, ; Mogensen & Divac, ; rat: Wikmark, Divac, & Weiss, ; cat: Divac, ; monkey: Rosvold & Szwarcbart, ; human: Müller & Knight, ), memory consolidation and learning (Hartmann & Güntürkün, ; Lengersdorf, Marks, Uengoer, Stüttgen, & Güntürkün, ; Lengersdorf, Stüttgen, Uengoer, & Güntürkün, ; Lissek, Diekamp, & Güntürkün, ; Lissek & Güntürkün, , ), and choice behavior (Kalenscher, Diekamp, & Gunturkun, ). Even more striking is that the PFC and NCL show a high degree of similarity in the neural code on both single neuron as well as neuronal population level.…”