The Emergent Engram: Multilevel Memory Trace Components and the Broader Interactions

Editorial

27 May 2022

Editorial: The Emergent Engram: Multilevel Memory Trace Components and the Broader Interactions

Bryan D. Devan

and

Robert J. McDonald

1,655 views

0 citations

Editors

Bryan D. Devan

Towson University

Robert James McDonald

University of Lethbridge

Impact

Review

21 October 2021

The Hebb Synapse Before Hebb: Theories of Synaptic Function in Learning and Memory Before Hebb (1949), With a Discussion of the Long-Lost Synaptic Theory of William McDougall

Richard E. Brown

, 1 more and

Jessica F. Garden

Since the work of Semon was rediscovered by Schacter in 1978, there has been a renewed interest is searching for the “engram” as the locus of memory in the brain and Hebb’s cell assembly has been equated with Semon’s engram. There have been many theories of memory involving some concept of synaptic change, culminating in the “Hebb Synapse” theory in 1949. However, Hebb said that the idea that any two cells or systems of cells that are repeatedly active at the same time will tend to become “associated,” was not his idea, but an old one. In this manuscript we give an overview of some of the theories of the neural basis of learning and memory before Hebb and describe the synaptic theory of William McDougall, which appears to have been an idea ahead of its time; so far ahead of its time that it was completely ignored by his contemporaries. We conclude by examining some critiques of McDougall’s theory of inhibition and with a short discussion on the fate of neuroscientists whose ideas were neglected when first presented but were accepted as important many decades later.

15,397 views

12 citations

(A) Illustration of the visual discrimination task. Rats were released from the start position and given a maximum of 60 s to swim to the S+ and escape from the water. A trial was considered correct if the rat swam to the S+ and climbed onto the hidden platform without first entering the S– quadrant. A trial was considered incorrect if the rat’s entire body (excluding tail) entered the S– quadrant. The S+ was counterbalanced within groups such that the rubber duck was the S+ for half the rats and the red buoy was the S+ for the other half. The location of S+ was also pseudo-randomly counterbalanced across trials within a swim session so that the rats would learn to swim to the S+ and not a discrete quadrant of the pool. (B) Illustration of the experimental design for the massed training condition (top) and the distributed training condition (bottom). After reaching criterion (defined as >80% accuracy over two consecutive days), all rats were given an additional 50 discrimination trials (each duck represents five trials). In the Massed Training condition, the rats received 50 additional trials over 5 days (10 trials per day). The Recent group received either sham or HPC surgery (Sx) 5–10 days following the last day of training, whereas the Remote group received sham or HPC surgery 10 weeks following the last day of training. In the Distributed training condition, the rats received the additional 50 training trials distributed over 10 weeks (five trials in one session per week). The distributed training group received sham or HPC surgery 5–10 days following their last day of training (approximately 10–11 weeks after reaching criterion). In all cases, the rats were given a minimum of 10 days recovery before testing for retention.

Original Research

15 November 2021

Overtraining Strengthens the Visual Discrimination Memory Trace Outside the Hippocampus in Male Rats

Hugo Lehmann

, 1 more and

Melissa J. Glenn

4,225 views

5 citations

Review

13 September 2021

The Engram’s Dark Horse: How Interneurons Regulate State-Dependent Memory Processing and Plasticity

Frank Raven

and

Sara J. Aton

Interneuron circuit motifs and their regulation by state. A conserved interneuron motif (present throughout hippocampus and neocortex) is shown in the mouse CA1. PV+ and SST+ interneurons provide inhibitory GABAergic input to principal (glutamatergic) cells’ (PCs’) soma/axon initial segment and dendrites, respectively. VIP+ interneurons inhibit SST+ interneurons in the circuit. Left: During a period of post-learning sleep, principal cells and PV+ interneurons generally become more active (Ognjanovski et al., 2014), while SST+ interneurons are relatively quiescent (due to lower acetylcholine-mediated activation in NREM sleep) (Delorme et al., 2021). Some principal neurons (engram neurons) will become selectively more active, and may form new and/or stronger synaptic connections (Clawson et al., 2021). PV+ interneurons promote more coherent NREM and REM sleep oscillations (Ognjanovski et al., 2017, 2018). All these features are essential components of sleep-dependent memory consolidation. Right: When learning is followed by SD, SST+ interneurons shown increased activity in response to higher acetylcholine levels (Delorme et al., 2021). VIP+ interneurons may also have reduced activation, reducing inhibitory input to SST+ interneurons. This leads to suppression of firing in surrounding principal neurons (Delorme et al., 2021). As a result, dendritic spines on engram neurons (and other principal neurons) will be reduced and connections between them will be weakened (Havekes et al., 2016; Raven et al., 2019; Havekes and Aton, 2020), which impairs memory consolidation.

Brain states such as arousal and sleep play critical roles in memory encoding, storage, and recall. Recent studies have highlighted the role of engram neurons–populations of neurons activated during learning–in subsequent memory consolidation and recall. These engram populations are generally assumed to be glutamatergic, and the vast majority of data regarding the function of engram neurons have focused on glutamatergic pyramidal or granule cell populations in either the hippocampus, amygdala, or neocortex. Recent data suggest that sleep and wake states differentially regulate the activity and temporal dynamics of engram neurons. Two potential mechanisms for this regulation are either via direct regulation of glutamatergic engram neuron excitability and firing, or via state-dependent effects on interneuron populations–which in turn modulate the activity of glutamatergic engram neurons. Here, we will discuss recent findings related to the roles of interneurons in state-regulated memory processes and synaptic plasticity, and the potential therapeutic implications of understanding these mechanisms.

13,135 views

16 citations

Original Research

03 March 2021

Sleep Facilitates Problem Solving With No Additional Gain Through Targeted Memory Reactivation

Felipe Beijamini

, 3 more and

Susanne Diekelmann

12,831 views

3 citations

Original Research

28 April 2021

Transient Inactivation of the Medial Prefrontal Cortex and Ventral Hippocampus Impairs Active Place Avoidance Retrieval on a Rotating Arena

Daniela Cernotova

, 1 more and

Jan Svoboda

3,601 views

3 citations

Place and response learning in the eight-arm radial maze. (A) In the “win-stay” radial maze task, light cues signal whether food is available at the end of each arm. This task promotes S-R response learning to the extent that the light cues (S) become associated with approach behavior (R). (B) In the win-shift radial maze, a rat must employ extra-maze spatial cues to locate food and avoid re-entries into arms in which food was already retrieved, thus promoting the use of place learning. (C) A virtual 4/8 dual-solution version of the radial maze may be employed to examine the relative use of place and response learning in human subjects. Each trial of this task is divided into two parts (Part 1 and Part 2). During Part 1, four of the eight arms are blocked with a wall, and the participant is instructed to enter the four open arms and retrieve hidden reward objects. During Part 2, all of the arms are open, and the participant is instructed to retrieve the remaining reward objects from the arms that were previously blocked. To avoid arm re-entries, the participants may employ a place learning strategy (i.e., refer to extra-maze spatial cues to guide behavior to the correct arms) or a response learning strategy (i.e., memorizing a series of egocentric responses leading to the correct arms). During a subsequent probe trial, the extra-maze spatial cues are blocked from view, preventing the use of a place strategy. Therefore, more errors during this probe trial suggest the use of a place strategy, whereas fewer errors suggest the use of a response strategy (images from Bohbot et al., 2012). (D) A 4-year-old child searches for rewards in a place learning version of the eight-arm radial maze (image from Overman et al., 1996).

Review

11 February 2021

Place vs. Response Learning: History, Controversy, and Neurobiology

Jarid Goodman

The present article provides a historical review of the place and response learning plus-maze tasks with a focus on the behavioral and neurobiological findings. The article begins by reviewing the conflict between Edward C. Tolman’s cognitive view and Clark L. Hull’s stimulus-response (S-R) view of learning and how the place and response learning plus-maze tasks were designed to resolve this debate. Cognitive learning theorists predicted that place learning would be acquired faster than response learning, indicating the dominance of cognitive learning, whereas S-R learning theorists predicted that response learning would be acquired faster, indicating the dominance of S-R learning. Here, the evidence is reviewed demonstrating that either place or response learning may be dominant in a given learning situation and that the relative dominance of place and response learning depends on various parametric factors (i.e., amount of training, visual aspects of the learning environment, emotional arousal, et cetera). Next, the neurobiology underlying place and response learning is reviewed, providing strong evidence for the existence of multiple memory systems in the mammalian brain. Research has indicated that place learning is principally mediated by the hippocampus, whereas response learning is mediated by the dorsolateral striatum. Other brain regions implicated in place and response learning are also discussed in this section, including the dorsomedial striatum, amygdala, and medial prefrontal cortex. An exhaustive review of the neurotransmitter systems underlying place and response learning is subsequently provided, indicating important roles for glutamate, dopamine, acetylcholine, cannabinoids, and estrogen. Closing remarks are made emphasizing the historical importance of the place and response learning tasks in resolving problems in learning theory, as well as for examining the behavioral and neurobiological mechanisms of multiple memory systems. How the place and response learning tasks may be employed in the future for examining extinction, neural circuits of memory, and human psychopathology is also briefly considered.

18,360 views

39 citations