scholarly journals Rapid synaptic plasticity contributes to a learned conjunctive code of position and choice-related information in the hippocampus

2021 ◽  
Author(s):  
Nelson Spruston ◽  
Xinyu Zhao ◽  
Ching-Lung Hsu
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Brain Regions ◽  
Induced Response ◽  
Population Code ◽  
Ca1 Pyramidal Neurons ◽  
Related Information ◽  
Plateau Potential ◽  
Whole Cell Recordings

To successfully perform goal-directed navigation, animals must know where they are and what they are doing, e.g., looking for water, bringing food back to the nest, or escaping from a predator. Hippocampal neurons code for these critical variables conjunctively, but little is known about how this where/what code is formed or flexibly routed to other brain regions. To address these questions, we performed intracellular whole-cell recordings in mouse CA1 during a cued, two-choice virtual navigation task. We demonstrate that plateau potentials in CA1 pyramidal neurons rapidly strengthen synaptic inputs carrying conjunctive information about position and choice. Plasticity-induced response fields were modulated by cues only in animals previously trained to collect rewards based on these cues. Thus, we reveal that gradual learning is required for the formation of a conjunctive population code, upstream of CA1, while plateau-potential-induced synaptic plasticity in CA1 enables flexible routing of the code to downstream brain regions.

scholarly journals Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Il Hwan Kim ◽  
Hong Wang ◽  
Scott H Soderling ◽  
Ryohei Yasuda
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Conditional Knockout ◽  
Remote Memory ◽  
Memory Recall ◽  
Ca1 Pyramidal Neurons ◽  
Memory Acquisition

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.

scholarly journals Local autocrine signaling of IGF1 synthesized and released by CA1 pyramidal neurons regulates plasticity of dendritic spines

2021 ◽  
Author(s):  
Xun Tu ◽  
Anant Jain ◽  
Helena Decker ◽  
Ryohei Yasuda
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Brain Regions ◽  
Dependent Manner ◽  
Autocrine Signaling ◽  
Ca1 Pyramidal Neurons ◽  
Igf1 Receptor ◽  
Activity Dependent

Insulin-like growth factor 1 (IGF1) regulates hippocampal plasticity, learning, and memory. While circulating, liver-derived IGF1 is known to play an essential role in hippocampal function and plasticity, IGF1 is also synthesized in multiple brain regions, including the hippocampus. However, little is known about the role of hippocampus-derived IGF1 in synaptic plasticity, the type of cells that may provide relevant IGF1, and the spatiotemporal dynamics of IGF1 signaling. Here, using a new FRET sensor for IGF1 signaling, we show that IGF1 in the hippocampus is primarily synthesized in CA1 pyramidal neurons and released in an activity-dependent manner in mice. The local IGF1 release from dendritic spines triggers local autocrine IGF1 receptor activation on the same spine, regulating structural and electrophysiological plasticity of the activated spine. Thus, our study demonstrates a novel mechanism underlying synaptic plasticity by the synthesis and autocrine signaling of IGF1 specific to CA1 pyramidal neurons.

scholarly journals Early Life Vitamin C Deficiency Does Not Alter Morphology of Hippocampal CA1 Pyramidal Neurons or Markers of Synaptic Plasticity in a Guinea Pig Model

Nutrients ◽  
2018 ◽  
Vol 10 (6) ◽  
pp. 749 ◽  
Author(s):  
Stine Hansen ◽  
Jane Jørgensen ◽  
Jens Nyengaard ◽  
Jens Lykkesfeldt ◽  
Pernille Tveden-Nyborg
Keyword(s):  
Synaptic Plasticity ◽  
Vitamin C ◽  
Guinea Pig ◽  
Early Life ◽  
Pyramidal Neurons ◽  
Pig Model ◽  
Vitamin C Deficiency ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Guinea Pig Model

Dichotomy of Action-Potential Backpropagation in CA1 Pyramidal Neuron Dendrites

2001 ◽  
Vol 86 (6) ◽  
pp. 2998-3010 ◽  
Author(s):  
Nace L. Golding ◽  
William L. Kath ◽  
Nelson Spruston
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Resting Potential ◽  
Model Parameters ◽  
Voltage Sensitivity ◽  
Whole Cell ◽  
Ca1 Pyramidal Neurons ◽  
Whole Cell Recordings

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 μm from the soma, single backpropagating action potentials exhibit <50% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 μm from the soma, action potentials in most cells backpropagated either strongly (26–42% attenuation; n = 9/20) or weakly (71–87% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300–410 μm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.

scholarly journals Development of dendritic tonic GABAergic inhibition regulates excitability and plasticity in CA1 pyramidal neurons

2014 ◽  
Vol 112 (2) ◽  
pp. 287-299 ◽  
Author(s):  
Martine R. Groen ◽  
Ole Paulsen ◽  
Enrique Pérez-Garci ◽  
Thomas Nevian ◽  
J. Wortel ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Action Potential ◽  
Pyramidal Neurons ◽  
Spike Timing ◽  
Tonic Inhibition ◽  
Developmental Changes ◽  
Gabaergic Inhibition ◽  
Gaba A ◽  
Ca1 Pyramidal Neurons ◽  
Mature Neurons

Synaptic plasticity rules change during development: while hippocampal synapses can be potentiated by a single action potential pairing protocol in young neurons, mature neurons require burst firing to induce synaptic potentiation. An essential component for spike timing-dependent plasticity is the backpropagating action potential (BAP). BAP along the dendrites can be modulated by morphology and ion channel composition, both of which change during late postnatal development. However, it is unclear whether these dendritic changes can explain the developmental changes in synaptic plasticity induction rules. Here, we show that tonic GABAergic inhibition regulates dendritic action potential backpropagation in adolescent, but not preadolescent, CA1 pyramidal neurons. These developmental changes in tonic inhibition also altered the induction threshold for spike timing-dependent plasticity in adolescent neurons. This GABAergic regulatory effect on backpropagation is restricted to distal regions of apical dendrites (>200 μm) and mediated by α5-containing GABA(A) receptors. Direct dendritic recordings demonstrate α5-mediated tonic GABA(A) currents in adolescent neurons which can modulate BAPs. These developmental modulations in dendritic excitability could not be explained by concurrent changes in dendritic morphology. To explain our data, model simulations propose a distally increasing or localized distal expression of dendritic α5 tonic inhibition in mature neurons. Overall, our results demonstrate that dendritic integration and plasticity in more mature dendrites are significantly altered by tonic α5 inhibition in a dendritic region-specific and developmentally regulated manner.

scholarly journals Disinhibitory and neuromodulatory regulation of hippocampal synaptic plasticity

2020 ◽  
Author(s):  
Inês Guerreiro ◽  
Zhenglin Gu ◽  
Jerrel L. Yakel ◽  
Boris S. Gutkin
Keyword(s):  
Synaptic Plasticity ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
General Mechanism ◽  
Excitatory Synapses ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Synaptic Plasticity ◽  
Local Circuitry ◽  
Feedforward Inhibition

AbstractHippocampal synaptic plasticity, particularly in the Schaffer collateral (SC) to CA1 pyramidal excitatory transmission, is considered as the cellular mechanism underlying learning. The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Our recent experiments showed that repeated cholinergic activation of α7 nACh receptors expressed in oriens-lacunosum-moleculare (OLMα2) interneurons could induce LTP in SC-CA1 synapses, likely through disinhibition by inhibiting stratum radiatum (s.r.) interneurons that provide feedforward inhibition onto CA1 pyramidal neurons, revealing a potential mechanism for local interneurons to regulate SC-CA1 synaptic plasticity. Here, we pair in vitro studies with biophysically-based modeling to uncover the mechanisms through which cholinergic-activated GABAergic interneurons can disinhibit CA1 pyramidal cells, and how repeated disinhibition modulates hippocampal plasticity at the excitatory synapses. We found that α7 nAChR activation increases OLM activity. OLM neurons, in turn inhibit the fast-spiking interneurons that provide feedforward inhibition onto CA1 pyramidal neurons. This disinhibition, paired with tightly timed SC stimulation, can induce potentiation at the excitatory synapses of CA1 pyramidal neurons. Our work further describes the pairing of disinhibition with SC stimulation as a general mechanism for the induction of hippocampal synaptic plasticity.Disinhibition of the excitatory synapses, paired with SC stimulation, leads to increased NMDAR activation and intracellular calcium concentration sufficient to upregulate AMPAR permeability and potentiate the synapse. Repeated paired disinhibition of the excitatory synapse leads to larger and longer lasting increases of the AMPAR permeability. Our study thus provides a novel mechanism for inhibitory interneurons to directly modify glutamatergic synaptic plasticity. In particular, we show how cholinergic action on OLM interneurons can down-regulate the GABAergic signaling onto CA1 pyramidal cells, and how this shapes local plasticity rules. We identify paired disinhibition with SC stimulation as a general mechanism for the induction of hippocampal synaptic plasticity.

scholarly journals FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kirsty Sawicka ◽  
Caryn R Hale ◽  
Christopher Y Park ◽  
John J Fak ◽  
Jodi E Gresack ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Rna Binding ◽  
Fragile X ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Cell Type ◽  
Ca1 Pyramidal Neurons ◽  
Mrna Targets ◽  
Specific Regulation

Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease pathophysiology. Here we use conditional tagging of FMRP and CLIP (FMRP cTag CLIP) to examine FMRP mRNA targets in hippocampal CA1 pyramidal neurons, a critical cell type for learning and memory relevant to FXS phenotypes. Integrating these data with analysis of ribosome-bound transcripts in these neurons revealed CA1-enriched binding of autism-relevant mRNAs, and CA1-specific regulation of transcripts encoding circadian proteins. This contrasted with different targets in cerebellar granule neurons, and was consistent with circadian defects in hippocampus-dependent memory in Fmr1 knockout mice. These findings demonstrate differential FMRP-dependent regulation of mRNAs across neuronal cell types that may contribute to phenotypes such as memory defects and sleep disturbance associated with FXS.

scholarly journals Enhanced Neuronal Damage After Ischemic Insults in Mice Lacking Kir6.2-Containing ATP-Sensitive K+ Channels

2006 ◽  
Vol 95 (4) ◽  
pp. 2590-2601 ◽  
Author(s):  
Hong-Shuo Sun ◽  
Zhong-Ping Feng ◽  
Takashi Miki ◽  
Susumu Seino ◽  
Robert J. French
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Hippocampal Slices ◽  
Immunocytochemical Staining ◽  
Sulfonylurea Receptor ◽  
Ca1 Pyramidal Neurons

Adenosine triphosphate (ATP)–sensitive potassium (KATP) channels, incorporating Kir6.x and sulfonylurea receptor subunits, are weak inward rectifiers that are thought to play a role in neuronal protection from ischemic insults. However, the involvement of Kir6.2-containing KATP channel in hippocampus and neocortex has not been tested directly. To delineate the physiological roles of Kir6.2 channels in the CNS, we used knockout (KO) mice that do not express Kir6.2. Immunocytochemical staining demonstrated that Kir6.2 protein was expressed robustly in hippocampal neurons of the wild-type (WT) mice and absent in the KO. To examine neuronal sensitivity to metabolic stress in vitro, and to ischemia in vivo, we 1) exposed hippocampal slices to transient oxygen and glucose deprivation (OGD) and 2) produced focal cerebral ischemia by middle cerebral artery occlusion (MCAO). Both slice and whole animal studies showed that neurons from the KO mice were severely damaged after anoxia or ischemia, whereas few injured neurons were observed in the WT, suggesting that Kir6.2 channels are necessary to protect neurons from ischemic insults. Membrane potential recordings from the WT CA1 pyramidal neurons showed a biphasic response to OGD; a brief hyperpolarization was followed by a small depolarization during OGD, with complete recovery within 30 min after returning to normoxic conditions. By contrast, CA1 pyramidal neurons from the KO mice were irreversibly depolarized by OGD exposure, without any preceding hyperpolarization. These data suggest that expression of Kir6.2 channels prevents prolonged depolarization of neurons resulting from acute hypoxic or ischemic insults, and thus protects these central neurons from the injury.

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