-
Neuron Oct 2023Neuronal activity during experience is thought to induce plastic changes within the hippocampal network that underlie memory formation, although the extent and details...
Neuronal activity during experience is thought to induce plastic changes within the hippocampal network that underlie memory formation, although the extent and details of such changes in vivo remain unclear. Here, we employed a temporally precise marker of neuronal activity, CaMPARI2, to label active CA1 hippocampal neurons in vivo, followed by immediate acute slice preparation and electrophysiological quantification of synaptic properties. Recently active neurons in the superficial sublayer of stratum pyramidale displayed larger post-synaptic responses at excitatory synapses from area CA3, with no change in pre-synaptic release probability. In contrast, in vivo activity correlated with weaker pre- and post-synaptic excitatory weights onto pyramidal cells in the deep sublayer. In vivo activity of deep and superficial neurons within sharp-wave/ripples was bidirectionally changed across experience, consistent with the observed changes in synaptic weights. These findings reveal novel, fundamental mechanisms through which the hippocampal network is modified by experience to store information.
Topics: CA3 Region, Hippocampal; Hippocampus; Neurons; Pyramidal Cells; Synapses; CA1 Region, Hippocampal
PubMed: 37689058
DOI: 10.1016/j.neuron.2023.08.014 -
Neuropsychopharmacology : Official... Jul 2023Pharmacological manipulation of mGluR5 has showed that mGluR5 is implicated in the pathophysiology of anxiety and mGluR5 has been proposed as a potential drug target for...
Pharmacological manipulation of mGluR5 has showed that mGluR5 is implicated in the pathophysiology of anxiety and mGluR5 has been proposed as a potential drug target for anxiety disorders. Nevertheless, the mechanism underlying the mGluR5 involvement in stress-induced anxiety-like behavior remains largely unknown. Here, we found that chronic restraint stress induced anxiety-like behavior and decreased the expression of mGluR5 in hippocampal CA1. Specific knockdown of mGluR5 in hippocampal CA1 pyramidal neurons produced anxiety-like behavior. Furthermore, both chronic restraint stress and mGluR5 knockdown impaired inhibitory synaptic inputs in hippocampal CA1 pyramidal neurons. Notably, positive allosteric modulator of mGluR5 rescued stress-induced anxiety-like behavior and restored the inhibitory synaptic inputs. These findings point to an essential role for mGluR5 in hippocampal CA1 pyramidal neurons in mediating stress-induced anxiety-like behavior.
Topics: Hippocampus; Pyramidal Cells; Anxiety; CA1 Region, Hippocampal
PubMed: 36797374
DOI: 10.1038/s41386-023-01548-w -
Science Advances Aug 2023The insulin superfamily of peptides is essential for homeostasis as well as neuronal plasticity, learning, and memory. Here, we show that insulin-like growth factors 1...
The insulin superfamily of peptides is essential for homeostasis as well as neuronal plasticity, learning, and memory. Here, we show that insulin-like growth factors 1 and 2 (IGF1 and IGF2) are differentially expressed in hippocampal neurons and released in an activity-dependent manner. Using a new fluorescence resonance energy transfer sensor for IGF1 receptor (IGF1R) with two-photon fluorescence lifetime imaging, we find that the release of IGF1 triggers rapid local autocrine IGF1R activation on the same spine and more than several micrometers along the stimulated dendrite, regulating the plasticity of the activated spine in CA1 pyramidal neurons. In CA3 neurons, IGF2, instead of IGF1, is responsible for IGF1R autocrine activation and synaptic plasticity. Thus, our study demonstrates the cell type-specific roles of IGF1 and IGF2 in hippocampal plasticity and a plasticity mechanism mediated by the synthesis and autocrine signaling of IGF peptides in pyramidal neurons.
Topics: Autocrine Communication; Dendritic Spines; Hippocampus; Neuronal Plasticity; Pyramidal Cells
PubMed: 37531435
DOI: 10.1126/sciadv.adg0666 -
Nature Communications Sep 2023Excitatory spiny stellate neurons are prominently featured in the cortical circuits of sensory modalities that provide high salience and high acuity representations of...
Excitatory spiny stellate neurons are prominently featured in the cortical circuits of sensory modalities that provide high salience and high acuity representations of the environment. These specialized neurons are considered developmentally linked to bottom-up inputs from the thalamus, however, the molecular mechanisms underlying their diversification and function are unknown. Here, we investigated this in mouse somatosensory cortex, where spiny stellate neurons and pyramidal neurons have distinct roles in processing whisker-evoked signals. Utilizing spatial transcriptomics, we identified reciprocal patterns of gene expression which correlated with these cell-types and were linked to innervation by specific thalamic inputs during development. Genetic manipulation that prevents the acquisition of spiny stellate fate highlighted an important role for these neurons in processing distinct whisker signals within functional cortical columns, and as a key driver in the formation of specific whisker-related circuits in the cortex.
Topics: Animals; Vibrissae; Neurons; Pyramidal Cells; Neurites; Somatosensory Cortex; Thalamus
PubMed: 37770450
DOI: 10.1038/s41467-023-41749-x -
Philosophical Transactions of the Royal... Jul 2024Neurons are plastic. That is, they change their activity according to different behavioural conditions. This endows pyramidal neurons with an incredible computational... (Review)
Review
Neurons are plastic. That is, they change their activity according to different behavioural conditions. This endows pyramidal neurons with an incredible computational power for the integration and processing of synaptic inputs. Plasticity can be investigated at different levels of investigation within a single neuron, from spines to dendrites, to synaptic input. Although most of our knowledge stems from the brain slice preparation, plasticity plays a vital role during behaviour by providing a flexible substrate for the execution of appropriate actions in our ever-changing environment. Owing to advances in recording techniques, the plasticity of neurons and the neural networks in which they are embedded is now beginning to be realized in the intact brain. This review focuses on the structural and functional synaptic plasticity of pyramidal neurons with a specific focus on the latest developments from studies. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
Topics: Pyramidal Cells; Neuronal Plasticity; Animals; Brain; Long-Term Potentiation; Synapses; Humans
PubMed: 38853566
DOI: 10.1098/rstb.2023.0231 -
Science (New York, N.Y.) Mar 2024The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic... (Review)
Review
The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and "flash-and-freeze" electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations.
Topics: Mossy Fibers, Hippocampal; Presynaptic Terminals; Synaptic Transmission; CA3 Region, Hippocampal; Pyramidal Cells; Humans; Animals
PubMed: 38452088
DOI: 10.1126/science.adg6757 -
Neuron Oct 2023Efficient sensory processing requires the nervous system to adjust to ongoing features of the environment. In primary visual cortex (V1), neuronal activity strongly...
Efficient sensory processing requires the nervous system to adjust to ongoing features of the environment. In primary visual cortex (V1), neuronal activity strongly depends on recent stimulus history. Existing models can explain effects of prolonged stimulus presentation but remain insufficient for explaining effects observed after shorter durations commonly encountered under natural conditions. We investigated the mechanisms driving adaptation in response to brief (100 ms) stimuli in L2/3 V1 neurons by performing in vivo whole-cell recordings to measure membrane potential and synaptic inputs. We find that rapid adaptation is generated by stimulus-specific suppression of excitatory and inhibitory synaptic inputs. Targeted optogenetic experiments reveal that these synaptic effects are due to input-specific short-term depression of transmission between layers 4 and 2/3. Thus, brief stimulus presentation engages a distinct adaptation mechanism from that previously reported in response to prolonged stimuli, enabling flexible control of sensory encoding across a wide range of timescales.
Topics: Mice; Animals; Neurons; Sensation; Membrane Potentials; Visual Cortex; Synapses
PubMed: 37543037
DOI: 10.1016/j.neuron.2023.07.003 -
Cerebral Cortex (New York, N.Y. : 1991) May 2024The basic building block of the cerebral cortex, the pyramidal cell, has been shown to be characterized by a markedly different dendritic structure among layers,...
The basic building block of the cerebral cortex, the pyramidal cell, has been shown to be characterized by a markedly different dendritic structure among layers, cortical areas, and species. Functionally, differences in the structure of their dendrites and axons are critical in determining how neurons integrate information. However, within the human cortex, these neurons have not been quantified in detail. In the present work, we performed intracellular injections of Lucifer Yellow and 3D reconstructed over 200 pyramidal neurons, including apical and basal dendritic and local axonal arbors and dendritic spines, from human occipital primary visual area and associative temporal cortex. We found that human pyramidal neurons from temporal cortex were larger, displayed more complex apical and basal structural organization, and had more spines compared to those in primary sensory cortex. Moreover, these human neocortical neurons displayed specific shared and distinct characteristics in comparison to previously published human hippocampal pyramidal neurons. Additionally, we identified distinct morphological features in human neurons that set them apart from mouse neurons. Lastly, we observed certain consistent organizational patterns shared across species. This study emphasizes the existing diversity within pyramidal cell structures across different cortical areas and species, suggesting substantial species-specific variations in their computational properties.
Topics: Humans; Pyramidal Cells; Animals; Male; Female; Mice; Adult; Dendritic Spines; Temporal Lobe; Dendrites; Middle Aged; Axons; Species Specificity
PubMed: 38745556
DOI: 10.1093/cercor/bhae180 -
Biological Psychiatry Aug 2023Parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acidergic) cells provide robust perisomatic inhibition to neighboring pyramidal neurons and regulate brain...
BACKGROUND
Parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acidergic) cells provide robust perisomatic inhibition to neighboring pyramidal neurons and regulate brain oscillations. Alterations in PV interneuron connectivity and function in the medial prefrontal cortex have been consistently reported in psychiatric disorders associated with cognitive rigidity, suggesting that PV cell deficits could be a core cellular phenotype in these disorders. The p75 neurotrophin receptor (p75NTR) regulates the time course of PV cell maturation in a cell-autonomous fashion. Whether p75NTR expression during postnatal development affects adult prefrontal PV cell connectivity and cognitive function is unknown.
METHODS
We generated transgenic mice with conditional knockout of p75NTR in postnatal PV cells. We analyzed PV cell connectivity and recruitment following a tail pinch by immunolabeling and confocal imaging in naïve mice or following p75NTR re-expression in preadolescent or postadolescent mice using Cre-dependent viral vectors. Cognitive flexibility was evaluated using behavioral tests.
RESULTS
PV cell-specific p75NTR deletion increased both PV cell synapse density and proportion of PV cells surrounded by perineuronal nets, a marker of mature PV cells, in adult medial prefrontal cortex, but not visual cortex. Both phenotypes were rescued by viral-mediated reintroduction of p75NTR in preadolescent, but not postadolescent, medial prefrontal cortex. Prefrontal cortical PV cells failed to upregulate c-Fos following a tail-pinch stimulation in adult conditional knockout mice. Finally, conditional knockout mice showed impaired fear memory extinction learning as well as deficits in an attention set-shifting task.
CONCLUSIONS
These findings suggest that p75NTR expression in adolescent PV cells contributes to the fine-tuning of their connectivity and promotes cognitive flexibility in adulthood.
Topics: Animals; Mice; Cognition; Interneurons; Mice, Knockout; Mice, Transgenic; Parvalbumins; Prefrontal Cortex; Receptor, Nerve Growth Factor
PubMed: 37120061
DOI: 10.1016/j.biopsych.2023.04.019 -
Communications Biology Dec 2023The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this...
The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this cortical-cortical connection and its functional importance. Here we investigate the cortical-cortical connection between the bilateral anterior cingulate cortex (ACC) by using the classic electrophysiological and optogenetic approach. We find that there is a direct synaptic projection from one side ACC to the contralateral ACC. Glutamate is the major excitatory transmitter for bilateral ACC connection, including projections to pyramidal cells in superficial (II/III) and deep (V/VI) layers of the ACC. Both AMPA and kainate receptors contribute to synaptic transmission. Repetitive stimulation of the projection also evoked postsynaptic Ca influx in contralateral ACC pyramidal neurons. Behaviorally, light activation of the ACC-ACC connection facilitated behavioral withdrawal responses to mechanical stimuli and noxious heat. In an animal model of neuropathic pain, light inhibitory of ACC-ACC connection reduces both primary and secondary hyperalgesia. Our findings provide strong direct evidence for the excitatory or facilitatory contribution of ACC-ACC connection to pain perception, and this mechanism may provide therapeutic targets for future treatment of chronic pain and related emotional disorders.
Topics: Mice; Animals; Gyrus Cinguli; Synaptic Transmission; Neuralgia; Pyramidal Cells; Glutamic Acid
PubMed: 38071375
DOI: 10.1038/s42003-023-05589-1