Histamine in the basolateral amygdala promotes inhibitory avoidance learning independently of hippocampus.
Recent discoveries demonstrated that recruitment of alternative brain circuits permits compensation of memory impairments following damage to brain regions specialized in integrating and/or storing specific memories, including both dorsal hippocampus and basolateral amygdala (BLA). Here, we first report that the integrity of the brain histaminergic system is necessary for long-term, but not for short-term memory of step-down inhibitory avoidance (IA). Second, we found that phosphorylation of cyclic adenosine monophosphate (cAMP) responsive-element-binding protein, a crucial mediator in long-term memory formation, correlated anatomically and temporally with histamine-induced memory retrieval, showing the active involvement of histamine function in CA1 and BLA in different phases of memory consolidation. Third, we found that exogenous application of histamine in either hippocampal CA1 or BLA of brain histamine-depleted rats, hence amnesic, restored long-term memory; however, the time frame of memory rescue was different for the two brain structures, short lived (immediately posttraining) for BLA, long lasting (up to 6 h) for the CA1. Moreover, long-term memory was formed immediately after training restoring of histamine transmission only in the BLA. These findings reveal the essential role of histaminergic neurotransmission to provide the brain with the plasticity necessary to ensure memorization of emotionally salient events, through recruitment of alternative circuits. Hence, our findings indicate that the histaminergic system comprises parallel, coordinated pathways that provide compensatory plasticity when one brain structure is compromised.
Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, 90610-000 Porto Alegre, RS, Brazil;
Fernando
F
Benetti
Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, 90610-000 Porto Alegre, RS, Brazil;
Cristiane Regina Guerino
CR
Furini
Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, 90610-000 Porto Alegre, RS, Brazil;
Jociane
J
de Carvalho Myskiw
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Universitá di Firenze, 50139 Firenze, Italy; and.
Gustavo
G
Provensi
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Universitá di Firenze, 50139 Firenze, Italy; and.
Maria Beatrice
MB
Passani
Dipartimento di Medicina Sperimentale e Clinica, Universitá di Firenze, 50134 Firenze, Italy.
Elisabetta
E
Baldi
Dipartimento di Medicina Sperimentale e Clinica, Universitá di Firenze, 50134 Firenze, Italy.
Corrado
C
Bucherelli
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Universitá di Firenze, 50139 Firenze, Italy; and.
Leonardo
L
Munari
Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, 90610-000 Porto Alegre, RS, Brazil; izquier@terra.com.br patrizio.blandina@unifi.it.
Ivan
I
Izquierdo
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Universitá di Firenze, 50139 Firenze, Italy; and izquier@terra.com.br patrizio.blandina@unifi.it.
Patrizio
P
Blandina
D000647:Amnesia / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning; D066272:Basolateral Nuclear Complex / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004644:Emotions; D006632:Histamine / Q000378:metabolism*; D008297:Male; D057567:Memory, Long-Term; D017551:Microdialysis; D023421:Models, Animal; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission
D017362:Cyclic AMP Response Element-Binding Protein; D006632:Histamine
amygdala; hippocampus; histamine; inhibitory avoidance; lateral ventricle