Septal cholinergic neurons gate hippocampal output to entorhinal cortex via oriens lacunosum moleculare interneurons

Haam, Juhee; Zhou, Jingheng; Cui, Guohong; Yakel, Jerrel L.

doi:10.1073/pnas.1712538115

Cited by 54 publications

(48 citation statements)

References 84 publications

(109 reference statements)

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“…between neurons representing a sequence) are plastic but weak during encoding, such that they have a negligible influence on the postsynaptic firing rate; and that the feedforward input dominates neuronal activity. These assumptions seem justified as Hasselmo (28) indicated that excitatory feedback connections may be suppressed during encoding to avoid interference from previously stored information (see also 30). Furthermore, neuromodulators facilitate long-term plasticity (reviewed, e.g., by 31), which also supports our assumptions.…”

Section: Wide Learning Windows (K σ)supporting

confidence: 81%

Synaptic learning rules for sequence learning

Reifenstein

Kempter

2020

Preprint

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Remembering the temporal order of a sequence of events is a task easily performed by humans in everyday life, but the underlying neuronal mechanisms are unclear. This problem is particularly intriguing as human behavior often proceeds on a time scale of seconds, which is in stark contrast to the much faster millisecond time-scale of neuronal processing in our brains. One long-held hypothesis in sequence learning suggests that a particular temporal fine-structure of neuronal activity-termed "phase precession"-enables the compression of slow behavioral sequences down to the fast time scale of the induction of synaptic plasticity. Using mathematical analysis and computer simulations, we find that phase precession can improve sequence learning tremendously and that the asymmetric part of the synaptic learning window is essential for temporal-order learning. To test these predictions, we suggest experiments that selectively alter phase precession or the learning window and evaluate memory of temporal order.

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Section: Wide Learning Windows (K σ)supporting

confidence: 81%

Synaptic learning rules for sequence learning

Reifenstein

Kempter

2020

Preprint

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“…This is consistent with our report that activation of MS cholinergic neurons decreased occurrence of high-frequency episodes in the HPC (17). Orienslacunosum moleculare cells may mediate these effects (58).…”

Section: Cellular Mechanismssupporting

confidence: 93%

Closed-loop stimulation of the medial septum terminates epileptic seizures

Takeuchi

Harangozó

Pedraza

et al. 2020

Preprint

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Temporal lobe epilepsy with distributed hippocampal seizure foci is often intractable and its secondary generalization might lead to sudden death. Early termination through spatially extensive hippocampal intervention is not feasible directly, due to its large size and irregular shape. In contrast, the medial septum (MS) is a promising target to govern hippocampal oscillations through its divergent connections to both hippocampi. Combining this 'proxy intervention' concept and precisely timed stimulation, we report here that closed-loop MS electrical stimulation can quickly terminate intrahippocampal seizures and suppress secondary generalization in a rat kindling model. Precise stimulus timing governed by internal seizure rhythms was essential. Cell-type-specific stimulation revealed that precisely timed activation of MS GABAergic neurons underlay the effects. Our concept of phase-targeted proxy stimulation for intervening pathological oscillations can be extrapolated to other neurological and psychiatric disorders, and its current embodiment can be directly translated into clinical application.

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“…This difference may be due to the timing of incoming inputs or the effect downstream of nicotinic versus metabotropic receptors (Haam and Yakel, 2017). The important role of cholinergic influence from the medial septum for OLM cell activity in learning and memory has recently been demonstrated (Haam et al, 2018). Our findings position intermediate OLM cells in a bidirectional role responding either to inhibitory inputs that improve learning or to excitatory inputs that prevent efficient learning, which possibly is provided by cholinergic action from the medial septum.…”

Section: Discussionmentioning

confidence: 58%

OLMα2 Cells Bidirectionally Modulate Learning

Siwani

França

Mikulovic

et al. 2018

Neuron

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Inhibitory interneurons participate in mnemonic processes. However, defined roles for identified interneuron populations are scarce. A subpopulation of oriens lacunosum-moleculare (OLM) interneurons genetically defined by the expression of the nicotinic receptor α2 subunit has been shown to gate information carried by either the temporoammonic pathway or Schaffer collaterals in vitro. Here we set out to determine whether selective modulation of OLMα2 cells in the intermediate CA1 affects learning and memory in vivo. Our data show that intermediate OLMα2 cells can either enhance (upon their inhibition) or impair (upon their activation) object memory encoding in freely moving mice, thus exerting bidirectional control. Moreover, we find that OLMα2 cell activation inhibits fear-related memories and that OLMα2 cells respond differently to nicotine in the dorsoventral axis. These results suggest that intermediate OLMα2 cells are an important component in the CA1 microcircuit regulating learning and memory processes. VIDEO ABSTRACT.

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Septal cholinergic neurons gate hippocampal output to entorhinal cortex via oriens lacunosum moleculare interneurons

Cited by 54 publications

References 84 publications

Synaptic learning rules for sequence learning

Synaptic learning rules for sequence learning

Closed-loop stimulation of the medial septum terminates epileptic seizures

OLMα2 Cells Bidirectionally Modulate Learning

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