Recoding a cocaine-place memory engram to a neutral engram in the hippocampus

Abstract

The hippocampus provides the brain’s memory system with a subset of neurons holding a map-like representation of each environment experienced. We found in mice that optogenetic-silencing those neurons active in an environment unmasked a subset of quiet neurons, enabling the emergence of an alternative map. This intervention applied in a cocaine-paired environment neutralized an otherwise long-lasting drug-place preference, showing that recoding a spatial memory engram can alleviate associated maladaptive behavior.

Locus coeruleus input to hippocampal CA3 drives single-trial learning of a novel context

“…Moreover, silencing the engram-bearing place cells active in a specific environment unmasked a subset of quiet neurons, which in turn enabled the emergence of an alternative map in those neurons. These data suggest two things: first, that a subset of CA1 engram cells are place cells, and second, that a subset of CA1 nonengram cells can turn into place cells when the original ensembles are unavailable (39). Our results indicate that LC neuromodulation supports these dynamic changes in a newly generated ensemble activity (Fig.…”

“…A recent study (39) demonstrated that c-Fos-tagged neurons in CA1 that were reactivated upon memory recall (i.e., engram cells) hold place fields. Moreover, silencing the engram-bearing place cells active in a specific environment unmasked a subset of quiet neurons, which in turn enabled the emergence of an alternative map in those neurons.…”

Cocaine Place Conditioning Strengthens Location-Specific Hippocampal Coupling to the Nucleus Accumbens

“…S2A) pairs cocaine with a spatial location defined relative to distal navigational cues, and proximal sensory cues were minimized and counterbalanced across cocaine/saline conditions. Under similar conditions, CPP has been shown to be dependent on dorsal hippocampus and not ventral hippocampus or amygdala (Ferbinteanu and McDonald, 2001; Meyers et al, 2003; Trouche et al, 2016). In CPP paradigms incorporating proximal sensory cues that differ between the cocaine and saline zones, NAc inputs from other structures such as the amygdala would likely be affected as well.…”

Pyramidal Cell-Interneuron Circuit Architecture and Dynamics in Hippocampal Networks

“…Neural circuit computation relies upon action potential transmission, and thus changes in transmission efficacy are vital for information storage. In particular, connectivity between excitatory neurons and local interneurons (feedback inhibition, including lateral inhibition), is believed to gate afferent drive (Fernandez-Ruiz et al, 2017, Milstein et al, 2015, Somogyi and Klausberger, 2005), control local synchrony (Stark et al, 2014), and dictate competitive interactions within the excitatory population (Buzsaki, 2010, Trouche et al, 2016). Therefore, a mechanistic understanding of neural circuit operations requires not only connectomic mapping of circuit elements, but also the elucidation of the parameters that affect the dynamic properties of individual synaptic connections that support circuit computation.…”

“…Additionally, we found that a diversity of short-term facilitation and short-term depression dynamics were simultaneously expressed by different connections of single presynaptic and postsynaptic neurons. Given that inhibition controls the dynamics of pyramidal cell activity, these findings have important implications for the organization and construction of cell assemblies (Buzsaki, 2010, Dupret et al, 2013, Trouche et al, 2016). …”