Grand Challenge at the Frontiers of Synaptic Neuroscience

Sjöström, P. Jesper

doi:10.3389/fnsyn.2021.748937

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…As there are many different kinds of INs (Gouwens et al, 2020), there is thus an even larger set of synapse-typespecific forms of plasticity at E→I, I→E, and I→I connections. A relatively comprehensive collection of plasticity learning rules for a given brain region -known as a plasticitome (Sjöström, 2021) is therefore required to understand the role of plasticity in local circuits (McFarlan et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

The spike-timing-dependent plasticity of VIP interneurons in motor cortex

McFarlan,

Guo,

Gomez

et al. 2024

Front. Cell. Neurosci.

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The plasticity of inhibitory interneurons (INs) plays an important role in the organization and maintenance of cortical microcircuits. Given the many different IN types, there is an even greater diversity in synapse-type-specific plasticity learning rules at excitatory to excitatory (E→I), I→E, and I→I synapses. I→I synapses play a key disinhibitory role in cortical circuits. Because they typically target other INs, vasoactive intestinal peptide (VIP) INs are often featured in I→I→E disinhibition, which upregulates activity in nearby excitatory neurons. VIP IN dysregulation may thus lead to neuropathologies such as epilepsy. In spite of the important activity regulatory role of VIP INs, their long-term plasticity has not been described. Therefore, we characterized the phenomenology of spike-timing-dependent plasticity (STDP) at inputs and outputs of genetically defined VIP INs. Using a combination of whole-cell recording, 2-photon microscopy, and optogenetics, we explored I→I STDP at layer 2/3 (L2/3) VIP IN outputs onto L5 Martinotti cells (MCs) and basket cells (BCs). We found that VIP IN→MC synapses underwent causal long-term depression (LTD) that was presynaptically expressed. VIP IN→BC connections, however, did not undergo any detectable plasticity. Conversely, using extracellular stimulation, we explored E→I STDP at inputs to VIP INs which revealed long-term potentiation (LTP) for both causal and acausal timings. Taken together, our results demonstrate that VIP INs possess synapse-type-specific learning rules at their inputs and outputs. This suggests the possibility of harnessing VIP IN long-term plasticity to control activity-related neuropathologies such as epilepsy.

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Section: Introductionmentioning

confidence: 99%

The spike-timing-dependent plasticity of VIP interneurons in motor cortex

McFarlan,

Guo,

Gomez

et al. 2024

Front. Cell. Neurosci.

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“…However, revealing the complete functional form of such dependence has been challenging because the slow timescale of synaptic plasticity limits a broad survey over different input variables, and changes in synaptic weights that are output variables vary over the trials. 11 To extract the plasticity rules from sparse and noisy data, theoretical works proposed a broad range of models, from simple phenomenological or biologically inspired models 12 , 13 , 14 , 15 , 16 to more refined models accounting for complex biochemical processes. 17 , 18 , 19 The latter is more flexible as it better captures dependence on different physiological conditions but requires extensive parameter fitting.…”

Section: Introductionmentioning

confidence: 99%

Efficient inference of synaptic plasticity rule with Gaussian process regression

Chen¹,

Qin²,

Lim³

2023

iScience

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“…This article posits that neurons operate as self-contained adaptive filters, supporting this claim by mapping the neuron (left) to an equivalent circuit (middle), observing that this circuit implements an adaptive filter (right), and validating the circuit's function by experiments. revealed a diversity of overlapping and interacting plasticity mechanisms [26,45]. A limitation of experiments in vitro is that crucial parameters such as temperature, membrane potential, and calcium concentration often transcend their physiological ranges.…”

Section: Introductionmentioning

confidence: 99%

“…Experimental methods typically investigate neurons’ responses to stimuli and various biological manipulations such as ion channel blocking and genetic modifications. Since the first discovery of synaptic plasticity [4], experiments have revealed a diversity of overlapping and interacting plasticity mechanisms [26, 45]. A limitation of experiments in vitro is that crucial parameters such as temperature, membrane potential, and calcium concentration often transcend their physiological ranges.…”

Section: Introductionmentioning

confidence: 99%

“…A significant theoretical contribution showed that classical Hebbian plasticity alone leads to the saturation of synaptic weights and the ensuing loss of information [38, 3]. Subsequent experiments demonstrated the existence of additional, homeostatic mechanisms that prevent distortion and stabilize synaptic plasticity [50, 49]. Here, “homeostasis” refers to the neuron’s retaining a stable internal environment despite changes in external conditions.…”

Section: Introductionmentioning

confidence: 99%

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Explaining neuroplasticity using equivalent circuits: A mechanistic perspective

Nilsson

2023

Preprint

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This paper introduces a comprehensive mechanistic model of a neuron with plasticity that explains the creation of engrams, the biophysical correlates of memory. In the context of a single neuron, this means clarifying how information conveyed as time-varying input signals is processed, stored, and subsequently recalled. Moreover, the model addresses two additional, long-standing, specific biological problems: how Hebbian plasticity, which amplifies synaptic weight, integrates with homeostatic plasticity, which stabilizes it, and how to identify a concise learning rule for synapses. In this study, a biologically accurate Hodgkin-Huxley-style electric-circuit equivalent is derived through a one-to-one mapping from the known properties of ion channels. The dynamics of the synaptic cleft, which is often overlooked, is found to be essential in this process. Analysis of the model reveals a simple and concise learning rule, indicating that the neuron functions as an internal-feedback adaptive filter, which is commonly used in signal processing. Simulation results confirm the circuit's functionality, stability, and convergence, demonstrating that even a single neuron without external feedback can function as a potent signal processor. The article is interdisciplinary and spans a broad range of subjects within the realm of biophysics, including neurobiology, electronics, and signal processing.

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Grand Challenge at the Frontiers of Synaptic Neuroscience

Cited by 7 publications

References 48 publications

The spike-timing-dependent plasticity of VIP interneurons in motor cortex

The spike-timing-dependent plasticity of VIP interneurons in motor cortex

Efficient inference of synaptic plasticity rule with Gaussian process regression

Explaining neuroplasticity using equivalent circuits: A mechanistic perspective

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