Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits.

In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance Excitatory-Inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage.

Bifurcation analysis of a two-compartment hippocampal pyramidal cell model.

The Pinsky-Rinzel model is a non-smooth 2-compartmental CA3 pyramidal cell model that has been used widely within the field of neuroscience. Here we propose a modified (smooth) system that captures the qualitative behaviour of the original model, while allowing the use of available, numerical continuation methods to perform full-system bifurcation and fast-slow analysis. We study the bifurcation structure of the full system as a function of the applied current and the maximal calcium conductance. We identify the bifurcations that shape the transitions between resting, bursting and spiking behaviours, and which lead to the disappearance of bursting when the calcium conductance is reduced. Insights gained from this analysis, are then used to firstly illustrate how the irregular spiking activity found between bursting and stable spiking states, can be influenced by phase differences in the calcium and dendritic voltage, which lead to corresponding changes in the calcium-sensitive potassium current. Furthermore, we use fast-slow analysis to investigate the mechanisms of bursting and show that bursting in the model is dependent on the intermediately slow variable, calcium, while the other slow variable, the activation gate of the afterhyperpolarisation current, does not contribute to setting the intraburst dynamics but participates in setting the interburst interval. Finally, we discuss how some of the described bifurcations affect spiking behaviour, during sharp-wave ripples, in a larger network of Pinsky-Rinzel cells.

The overfitted brain hypothesis.

What is the purpose of dreaming? Many scientists have postulated a role for dreaming in learning, often with the aim of improving generative models. In this issue of Patterns, Erik Hoel proposes a novel hypothesis, namely, that dreaming provides a means to reduce overfitting. This hypothesis is interesting both for neuroscience and for the development of new machine-learning systems.

Neocortical inhibitory interneuron subtypes are differentially attuned to synchrony- and rate-coded information.

Neurons can carry information with both the synchrony and rate of their spikes. However, it is unknown whether distinct subtypes of neurons are more sensitive to information carried by synchrony versus rate, or vice versa. Here, we address this question using patterned optical stimulation in slices of somatosensory cortex from mouse lines labelling fast-spiking (FS) and regular-spiking (RS) interneurons. We used optical stimulation in layer 2/3 to encode a 1-bit signal using either the synchrony or rate of activity. We then examined the mutual information between this signal and the interneuron responses. We found that for a synchrony encoding, FS interneurons carried more information in the first five milliseconds, while both interneuron subtypes carried more information than excitatory neurons in later responses. For a rate encoding, we found that RS interneurons carried more information after several milliseconds. These data demonstrate that distinct interneuron subtypes in the neocortex have distinct sensitivities to synchrony versus rate codes.

Neuromodulation of the Feedforward Dentate Gyrus-CA3 Microcircuit.

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.