Dopamine Long-Term Memory Storage

Comemorando a Prata da Casa!... Science 21 August 2009: Vol. 325. no. 5943, pp. 1017 - 1020 DOI: 10.1126/science.1172545

Reports

Dopamine Controls Persistence of Long-Term Memory Storage

Janine I. Rossato,^1,2 Lia R. M. Bevilaqua,^1,2 Iván Izquierdo,^1,2 Jorge H. Medina,^1,3,4 Martín Cammarota^1,2,3,*

The paradigmatic feature of long-term memory (LTM) is its persistence. However, little is known about the mechanisms that make some LTMs last longer than others. In rats, a long-lasting fear LTM vanished rapidly when the D1 dopamine receptor antagonist SCH23390 was injected into the dorsal hippocampus 12 hours, but not immediately or 9 hours, after the fearful experience. Conversely, intrahippocampal application of the D1 agonist SK38393 at the same critical post-training time converted a rapidly decaying fear LTM into a persistent one. This effect was mediated by brain-derived neurotrophic factor and regulated by the ventral tegmental area (VTA). Thus, the persistence of LTM depends on activation of VTA/hippocampus dopaminergic connections and can be specifically modulated by manipulating this system at definite post-learning time points.

¹ Centro de Memória, Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
² Instituto Nacional de Neurociência Translacional, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil.
³ Instituto de Biología Celular y Neurociencias "Prof. Dr. Eduardo de Robertis," Universidad de Buenos Aires, Buenos Aires, Argentina.
⁴ Departamento de Fisiologia, Universidad de Buenos Aires, Buenos Aires, Argentina.

^* To whom correspondence should be addressed. E-mail: mcammaro@terra.com.br or martin.cammarota@pucrs.br

Relevant environmental changes trigger transient dopamine-dependent states in the hippocampus that favor memory encoding and synaptic potentiation, perhaps by attaching motivational connotations to experiences (1–4). The ventral tegmental area (VTA) is critical for assessing the significance of punishments and rewards (5), and it has been postulated that a VTA/hippocampus dopaminergic loop controls the entry of information into long-term memory (LTM) (6). Dopamine regulates the expression of proteins essential for the establishment of lasting neuronal plasticity, such as brain-derived neurotrophic factor (BDNF) (7). In rats, we recently demonstrated that in order to persist, fear LTM requires BDNF expression in the hippocampus 12 hours after training (8). We have now investigated the role of hippocampal dopamine and the VTA on LTM persistence./.../