Neuromodulation of the Feedforward Dentate Gyrus-CA3 Microcircuit

Abstract

The feedforward dentate gyrus-CA3 microcircuit in the hippocampus is thought to activate ensembles of CA3 pyramidal cells and interneurons to encode and retrieve episodic memories. The creation of these CA3 ensembles depends on neuromodulatory input and synaptic plasticity within this microcircuit. Here we review the mechanisms by which the neuromodulators aceylcholine, noradrenaline, dopamine, and serotonin reconfigure this microcircuit and thereby infer the net effect of these modulators on the processes of episodic memory encoding and retrieval.

Dopamine is a double-edged sword: Enhancing memory retrieval performance at the expense of metacognition

“…D2-autoreceptors are particularly abundant in the striatum (Ford, 2014) but also present in the hippocampus (Rocchetti et al, 2015) and amygdala (Bull et al, 1991) and although dopaminestimulating effects in response to D2-antagonists seem to be less extreme in these structures compared to the striatum (Garris and Wightman, 1995), the relative sparseness of DAT in the hippocampus (Kwon et al, 2008) might lead to longer-lasting dopamine effects in the hippocampus (Prince et al, 2016). In particular, such increased stimulation of the postsynaptic D1-like receptors prevailing in hippocampus and amygdala (Köhler et al, 1991;Okubo et al, 1999;Rocchetti et al, 2015) by the dopaminergic midbrain might have led to the improved memory discrimination, possibly mediated by an increased signal-to-noise ratio (Frank, 2005;Warren et al, 2016;Yousif et al, 2016) of the representation of episodic information in these mnemonic structures.…”

Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

“…The hippocampus is a hub for the encoding, updating and retrieval of episodic memories, enabling events to be placed into a context. Individual items of information from the neocortex are thought to be sparsely encoded and separated by strong lateral inhibition in the dentate gyrus before being assembled into larger memory representations within the recurrent CA3 network (Hasselmo, 2006; Prince et al, 2016). These memory representations are then transferred via the Schaffer collateral (SC) pathway to CA1 which also receives new sensory information directly from the entorhinal cortex layer III pyramidal neurons via the temporoammonic (TA) pathway enabling CA1 to compare and integrate the new information (Ahmed and Mehta, 2009; Eichenbaum, 2017; Takahashi and Magee, 2009; Witter, 1993).…”

Simulations of Learning, Memory, and Forgetting Processes with Model of CA1 Region of the Hippocampus

“…In this process pyramidal neurons located in the cerebral cortex or hippocampus get supplementary inputs from the excited emotion areas such as amygdaloid body, which might be perceived as an indirect supervised learning algorithm. The elementary mechanism for long-term potentiation induction requires presence of NMDA channels and removal of magnesium ions blockade to enable calcium ions influx through them [82,83]. This is accomplished by depolarization of postsynaptic region; however instant depolarization is dependent on history of input patterns.…”