AUTHORS: Sadegh Nabavi, Rocky Fox, Christophe D. Proulx, John Y. Lin, Roger Y. Tsien & Roberto Malinow
ABSTRACT: It has been proposed that memories are encoded by modification of synaptic strengths through cellular mechanisms such as long-term potentiation (LTP) and long-term depression (LTD)1. However, the causal link between these synaptic processes and memory has been difficult to demonstrate2. Here we show that fear conditioning3–8, a type of associative memory, can be inactivated and reactivated by LTD and LTP, respectively. We began by conditioning an animal to associate a foot shock with optogenetic stimulation of auditory inputs targeting the amygdala, a brain region known to be essential for fear conditioning3–8. Subsequent optogenetic delivery of LTDconditioning to the auditory input inactivatesmemory of the shock. Then subsequent optogenetic delivery of LTP conditioning to the auditory input reactivates memory of the shock. Thus, we have engineered inactivation and reactivation of a memory using LTD and LTP, supporting a causal link between these synaptic processes and memory.
AUTHORS: Bianca A Silva, Camilla Mattucci, Piotr Krzywkowski, Emanuele Murana, Anna Illarionova, Valery Grinevich, Newton S Canteras, Davide Ragozzino & Cornelius T Gross
ABSTRACT: The neural circuits mediating fear to naturalistic threats are poorly understood. We found that functionally independent populations of neurons in the ventromedial hypothalamus (VMH), a region that has been implicated in feeding, sex and aggression, are essential for predator and social fear in mice. Our results establish a critical role for VMH in fear and have implications
for selective intervention in pathological fear in humans.
AUTHORS: Juan Song, Jiaqi Sun, Jonathan Moss, Zhexing Wen, Gerald J Sun, Derek Hsu, Chun Zhong, Heydar Davoudi, Kimberly M Christian, Nicolas Toni, Guo-li Ming & Hongjun Song
ABSTRACT: Using immunohistology, electron microscopy, electrophysiology and optogenetics, we found that proliferating adult mouse hippocampal neural precursors received immature GABAergic synaptic inputs from parvalbumin-expressing interneurons. Recently shown to suppress adult quiescent neural stem cell activation, parvalbumin interneuron activation promoted newborn neuronal progeny survival and development. Our results suggest a niche mechanism involving parvalbumin interneurons that couples local circuit activity to the diametric regulation of two critical early phases of adult hippocampal neurogenesis.
AUTHORS: Vincent Pascoli, Jean Terrier, Julie Espallergues, Emmanuel Valjent, Eoin Cornelius O’Connor & Christian Luscher
ABSTRACT: Nucleus accumbens neurons serve to integrate information from cortical and limbic regions to direct behaviour. Addictive drugs are proposed to hijack this system, enabling drug-associated cues to trigger relapse to drug seeking. However, the connections affected and proof of causality remain to be established. Here we use a mouse model of delayed cueassociated cocaine seeking with ex vivo electrophysiology in optogenetically delineated circuits. We find that seeking correlates with rectifying AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor transmission and a reduced AMPA/NMDA (N-methyl-D-aspartate) ratio at medial prefrontal cortex (mPFC) to nucleus accumbens shell D1-receptor medium-sized spiny neurons (D1R-MSNs). In contrast, the AMPA/NMDA ratio increases at ventral hippocampus to D1R-MSNs. Optogenetic reversal of cocaine-evoked plasticity at both inputs abolishes seeking,whereas selective reversal at mPFC or ventral hippocampus synapses impairs response discrimination or reduces response vigour during seeking, respectively. Taken together, we describe how information integration in the nucleus accumbens is commandeered by cocaine at discrete synapses to allow relapse. Our approach holds promise for identifying synaptic causalities in other behavioural disorders.