Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology

By Michael E. Hasselmo, Eric Schnell. 1994

ACh may set the dynamics of cortical function to those appropriate for learning new information. In models of the putative associative memory function of piriform cortex, selective suppression of intrinsic but not afferent fiber synaptic transmission by ACh prevents recall of previous input from interfering with the learning of new input (Hasselmo, 1993). Selective cholinergic suppression may play a similar role in the hippocampal formation, where Schaffer collateral synapses in stratum radiatum (s. rad) may store associations between activity in region CA3 and the entorhinal cortex input to region CA1 terminating in stratum lacunosum-moleculare (s. l-m). A computational model of region CA1 predicts that for effective associative memory function of the Schaffer collaterals, cholinergic suppression of synaptic transmission should be stronger in s. rad than in s. l-m. In the hippocampal slice preparation, we tested the effect of the cholinergic agonist carbachol (0.01–500 microM) on synaptic transmission in s. rad and s. l-m. Stimulating and recording electrodes were simultaneously placed in both layers, allowing analysis of the effect of carbachol on synaptic potentials in both layers during the same perfusion in each slice. Carbachol produced a significantly stronger suppression of stimulus- evoked EPSPs in s. rad than in s. l-m at all concentrations greater than 1 microM. At 100 microM, EPSP initial slopes were suppressed by 89.1 +/- 3.0% in s. rad, but only by 40.1 +/- 4.1% in s. l-m. The muscarinic antagonist atropine (1 microM) blocked cholinergic suppression in both layers. These data support the hypothesis that synaptic modification of the Schaffer collaterals may store associations between activity in region CA3 and the afferent input to region CA1 from the entorhinal cortex. In simulations, feedback regulation of cholinergic modulation based on activity in region CA1 sets the appropriate dynamics of learning for novel associations, and recall for familiar associations.

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Citations in the corpus

Born to Learn: the Inspiration, Progress, and Future of Evolved Plastic Artificial Neural Networks (2017, background): “Modulatory chemicals such as acetylcholine (ACh), norepinephrine (NE), serotonin (5-HT) and dopamine (DA) appear to regulate a large variety of neural functions, from arousal and behavior (Harris-Warrick and Marder, 1991; Hasselmo and Schnell, 1994; Marder, 1996; Katz, 1995; Katz and Frost, 1996), t”
Generalization Through the Recurrent Interaction of Episodic Memories (2012, methodology): “Our assessment of the network’s performance is carried out, therefore, in “recall” mode, such that weights are fixed within a simulation, as in previous work (e.g., Hasselmo & Schnell, 1994; Wu & Levy, 2001).”
Novelty or Surprise? (2013, background): “It refers to the following processes (Hasselmo and Schnell, 1994; Kumaran and Maguire, 2007; Duncan et al., 2012): (a) familiar aspects of the percept (“lures”) actively recall previous memories on the basis of pattern-completion-like mechanisms, for example, an item recalls other items previously…”
A computational principle for hippocampal learning and neurogenesis (2005, background): “Hasselmo and Schnell (1994) have suggested that ACh selectively suppresses synaptic transmission in the Shaffer collaterals (denoted W (CA3,CA1) in our model) during learning, which would satisfy the assumption that the perforant path provides the dominant input to the CA1 region during learning.”
The role of acetylcholine in learning and memory. (2006, background): “Hasselmo ME, Schnell E: Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology.”
Switching between internal and external modes: A multiscale learning principle (2017, background): “Such evidence, in conjunction with evidence from in vitro studies (Hasselmo & Schnell, 1994), suggests that cholinergic modulation plays a central role in mediating the switching between bottom-up and top-down processing in the hippocampus.”
From modulated Hebbian plasticity to simple behavior learning through noise and weight saturation (2012, background): “Driven by biological findings, researchers have augmented their models with modulatory signals (Hasselmo and Schnell, 1994; Fellous and Linster, 1998; Ludvig et al., 2008) or attempted to model biological modulatory activities (Baxter et al.”
Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. (2005, unknown): “[66,67]).”
Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate-CA3 interactions. (1999, unknown): “into several models (Lynch and Ranger, 1992; Hasselmo and Schnell, 1994; Blum and Abbott, 1996; Levy, 1996).”
What is the function of hippocampal theta rhythm?—Linking behavioral data to phasic properties of field potential and unit recording data (2005, background): “Selective presynaptic inhibition of glutamatergic transmission by muscarinic cholinergic receptors at association fiber synapses could provide this mechanism (Hasselmo and Schnell, 1994).”
Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function (2009, background): “, perforant path) afferent inputs is considered important in switching between encoding and retrieval modes of associative memory systems (208, 364, 482).”
Metalearning and neuromodulation (2002, background): “Hasselmo and colleagues proposed the role of acetylcholine in controlling the modes of operation in the hippocampus and the cortex: memory storage with a high level of cholinergic input and memory retrieval with a low level of cholinergic input (Hasselmo & Bower, 1993; Hasselmo & Schnell, 1994).”
Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior (2012, background): “Neocortical ACh function has been linked to control of circuits underlying attention, cue detection, and memory (Hasselmo and Sarter, 2011).”