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Neuron Oct 2017Excitatory control of inhibitory neurons is poorly understood due to the difficulty of studying synaptic connectivity in vivo. We inferred such connectivity through...
Excitatory control of inhibitory neurons is poorly understood due to the difficulty of studying synaptic connectivity in vivo. We inferred such connectivity through analysis of spike timing and validated this inference using juxtacellular and optogenetic control of presynaptic spikes in behaving mice. We observed that neighboring CA1 neurons had stronger connections and that superficial pyramidal cells projected more to deep interneurons. Connection probability and strength were skewed, with a minority of highly connected hubs. Divergent presynaptic connections led to synchrony between interneurons. Synchrony of convergent presynaptic inputs boosted postsynaptic drive. Presynaptic firing frequency was read out by postsynaptic neurons through short-term depression and facilitation, with individual pyramidal cells and interneurons displaying a diversity of spike transmission filters. Additionally, spike transmission was strongly modulated by prior spike timing of the postsynaptic cell. These results bridge anatomical structure with physiological function.
Topics: Action Potentials; Animals; CA1 Region, Hippocampal; Female; Interneurons; Male; Mice; Mice, Transgenic; Nerve Net; Optogenetics; Pyramidal Cells; Random Allocation
PubMed: 29024669
DOI: 10.1016/j.neuron.2017.09.033 -
Nature Communications Oct 2022Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent...
Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase-followed by a prolonged decrease-in pyramidal cell activity under sustained feed-forward input. However, under feed-forward transient input, the primary motor to primary somatosensory cortex feedback facilitates bursting while lateromedial area to primary visual cortex feedback increases time precision. Our findings argue for multiple cortico-cortical feedback motifs implementing different dynamic non-linear operations.
Topics: Mice; Animals; Feedback; Interneurons; Pyramidal Cells; Vasoactive Intestinal Peptide
PubMed: 36302912
DOI: 10.1038/s41467-022-33883-9 -
Neurobiology of Learning and Memory Oct 2019The current review provides a historical perspective on the evolution of hypothesized mechanisms for senescent neurophysiology, focused on the CA1 region of the... (Review)
Review
The current review provides a historical perspective on the evolution of hypothesized mechanisms for senescent neurophysiology, focused on the CA1 region of the hippocampus, and the relationship of senescent neurophysiology to impaired hippocampal-dependent memory. Senescent neurophysiology involves processes linked to calcium (Ca) signaling including an increase in the Ca-dependent afterhyperpolarization (AHP), decreasing pyramidal cell excitability, hyporesponsiveness of N-methyl-D-aspartate (NMDA) receptor function, and a shift in Ca-dependent synaptic plasticity. Dysregulation of intracellular Ca and downstream signaling of kinase and phosphatase activity lies at the core of senescent neurophysiology. Ca-dysregulation involves a decrease in Ca influx through NMDA receptors and an increase release of Ca from internal Ca stores. Recent work has identified changes in redox signaling, arising in middle-age, as an initiating factor for senescent neurophysiology. The shift in redox state links processes of aging, oxidative stress and inflammation, with functional changes in mechanisms required for episodic memory. The link between age-related changes in Ca signaling, epigenetics and gene expression is an exciting area of research. Pharmacological and behavioral intervention, initiated in middle-age, can promote memory function by initiating transcription of neuroprotective genes and rejuvenating neurophysiology. However, with more advanced age, or under conditions of neurodegenerative disease, epigenetic changes may weaken the link between environmental influences and transcription, decreasing resilience of memory function.
Topics: Aging; Animals; CA1 Region, Hippocampal; Calcium Signaling; Cell Nucleus; Epigenesis, Genetic; Excitatory Postsynaptic Potentials; Humans; Membrane Potentials; Neuronal Plasticity; Pyramidal Cells; Receptors, N-Methyl-D-Aspartate
PubMed: 31394200
DOI: 10.1016/j.nlm.2019.107064 -
PLoS Computational Biology Feb 2022Hippocampal sharp wave/ripple oscillations are a prominent pattern of collective activity, which consists of a strong overall increase of activity with superimposed (140...
Hippocampal sharp wave/ripple oscillations are a prominent pattern of collective activity, which consists of a strong overall increase of activity with superimposed (140 - 200 Hz) ripple oscillations. Despite its prominence and its experimentally demonstrated importance for memory consolidation, the mechanisms underlying its generation are to date not understood. Several models assume that recurrent networks of inhibitory cells alone can explain the generation and main characteristics of the ripple oscillations. Recent experiments, however, indicate that in addition to inhibitory basket cells, the pattern requires in vivo the activity of the local population of excitatory pyramidal cells. Here, we study a model for networks in the hippocampal region CA1 incorporating such a local excitatory population of pyramidal neurons. We start by investigating its ability to generate ripple oscillations using extensive simulations. Using biologically plausible parameters, we find that short pulses of external excitation triggering excitatory cell spiking are required for sharp/wave ripple generation with oscillation patterns similar to in vivo observations. Our model has plausible values for single neuron, synapse and connectivity parameters, random connectivity and no strong feedforward drive to the inhibitory population. Specifically, whereas temporally broad excitation can lead to high-frequency oscillations in the ripple range, sparse pyramidal cell activity is only obtained with pulse-like external CA3 excitation. Further simulations indicate that such short pulses could originate from dendritic spikes in the apical or basal dendrites of CA1 pyramidal cells, which are triggered by coincident spike arrivals from hippocampal region CA3. Finally we show that replay of sequences by pyramidal neurons and ripple oscillations can arise intrinsically in CA1 due to structured connectivity that gives rise to alternating excitatory pulse and inhibitory gap coding; the latter denotes phases of silence in specific basket cell groups, which induce selective disinhibition of groups of pyramidal neurons. This general mechanism for sequence generation leads to sparse pyramidal cell and dense basket cell spiking, does not rely on synfire chain-like feedforward excitation and may be relevant for other brain regions as well.
Topics: Action Potentials; CA1 Region, Hippocampal; CA3 Region, Hippocampal; Dendrites; Hippocampus; Neurons; Pyramidal Cells; Synapses
PubMed: 35176028
DOI: 10.1371/journal.pcbi.1009891 -
Communications Biology Apr 2021The cortex processes information through intricate circuitry and outputs to multiple brain areas by different sets of pyramidal cells (PCs). PCs form intra- and...
The cortex processes information through intricate circuitry and outputs to multiple brain areas by different sets of pyramidal cells (PCs). PCs form intra- and inter-laminar subnetworks, depending on PC projection subtypes. However, it remains unknown how individual PC subtypes are involved in cortical network activity and, thereby, in distinct brain functions. Here, we examined the effects of optogenetic manipulations of specific PC subtypes on network activity in the motor cortex. In layer V, the beta/gamma frequency band of oscillation was evoked by photostimulation, depending on PC subtypes. Our experimental and simulation results suggest that oscillatory activity is generated in reciprocal connections between pyramidal tract (PT) and fast-spiking cells. A similar frequency band was also observed in local field potentials during a pattern learning task. Manipulation of PT cell activity affected beta/gamma band power and learning. Our results suggest that PT cell-dependent oscillations play important roles in motor learning.
Topics: Animals; Female; Learning; Male; Motor Activity; Motor Cortex; Neural Pathways; Optogenetics; Pyramidal Cells; Rats; Rats, Wistar
PubMed: 33888862
DOI: 10.1038/s42003-021-02010-7 -
Proceedings of the National Academy of... Mar 2022SignificanceChandelier cells (ChCs) are a unique type of GABAergic interneuron that form axo-axonic synapses exclusively on the axon initial segment (AIS) of neocortical...
SignificanceChandelier cells (ChCs) are a unique type of GABAergic interneuron that form axo-axonic synapses exclusively on the axon initial segment (AIS) of neocortical pyramidal neurons (PyNs), allowing them to exert powerful yet precise control over PyN firing and population output. The importance of proper ChC function is further underscored by the association of ChC connectivity defects with various neurological conditions. Despite this, the cellular mechanisms governing ChC axo-axonic synapse formation remain poorly understood. Here, we identify microglia as key regulators of ChC axonal morphogenesis and AIS synaptogenesis, and show that disease-induced aberrant microglial activation perturbs proper ChC synaptic development/connectivity in the neocortex. In doing so, such findings highlight the therapeutic potential of manipulating microglia to ensure proper brain wiring.
Topics: Animals; Axon Initial Segment; GABAergic Neurons; Mice; Microglia; Pyramidal Cells; Synapses
PubMed: 35263225
DOI: 10.1073/pnas.2114476119 -
The Journal of Neuroscience : the... Jul 2020Plasticity within hippocampal circuits is essential for memory functions. The hippocampal CA2/CA3 region is thought to be able to rapidly store incoming information by...
Plasticity within hippocampal circuits is essential for memory functions. The hippocampal CA2/CA3 region is thought to be able to rapidly store incoming information by plastic modifications of synaptic weights within its recurrent network. High-frequency spike-bursts are believed to be essential for this process, by serving as triggers for synaptic plasticity. Given the diversity of CA2/CA3 pyramidal neurons, it is currently unknown whether and how burst activity, assessed during natural behavior, relates to principal cell heterogeneity. To explore this issue, we juxtacellularly recorded the activity of single CA2/CA3 neurons from freely-moving male mice, exploring a familiar environment. In line with previous work, we found that spatial and temporal activity patterns of pyramidal neurons correlated with their topographical position. Morphometric analysis revealed that neurons with a higher proportion of distal dendritic length displayed a higher tendency to fire spike-bursts. We propose that the dendritic architecture of pyramidal neurons might determine burst-firing by setting the relative amount of distal excitatory inputs from the entorhinal cortex. High-frequency spike-bursts are thought to serve fundamental computational roles within neural circuits. Within hippocampal circuits, spike-bursts are believed to serve as potent instructive signals, which increase the efficiency of information transfer and induce rapid modifications of synaptic efficacies. In the present study, by juxtacellularly recording and labeling single CA2/CA3 neurons in freely-moving mice, we explored whether and how burst propensity relates to pyramidal cell heterogeneity. We provide evidence that, within the CA2/CA3 region, neurons with higher proportion of distal dendritic length display a higher tendency to fire spike-bursts. Thus, the relative amount of entorhinal inputs, arriving onto the distal dendrites, might determine the burst propensity of individual CA2/CA3 neurons during natural behavior.
Topics: Action Potentials; Animals; CA2 Region, Hippocampal; CA3 Region, Hippocampal; Male; Mice; Mice, Inbred C57BL; Movement; Pyramidal Cells
PubMed: 32554511
DOI: 10.1523/JNEUROSCI.0099-20.2020 -
Scientific Data May 2023The apical dendrites of pyramidal neurons in sensory cortex receive primarily top-down signals from associative and motor regions, while cell bodies and nearby dendrites...
The apical dendrites of pyramidal neurons in sensory cortex receive primarily top-down signals from associative and motor regions, while cell bodies and nearby dendrites are heavily targeted by locally recurrent or bottom-up inputs from the sensory periphery. Based on these differences, a number of theories in computational neuroscience postulate a unique role for apical dendrites in learning. However, due to technical challenges in data collection, little data is available for comparing the responses of apical dendrites to cell bodies over multiple days. Here we present a dataset collected through the Allen Institute Mindscope's OpenScope program that addresses this need. This dataset comprises high-quality two-photon calcium imaging from the apical dendrites and the cell bodies of visual cortical pyramidal neurons, acquired over multiple days in awake, behaving mice that were presented with visual stimuli. Many of the cell bodies and dendrite segments were tracked over days, enabling analyses of how their responses change over time. This dataset allows neuroscientists to explore the differences between apical and somatic processing and plasticity.
Topics: Animals; Mice; Cell Body; Dendrites; Neurons; Pyramidal Cells; Visual Cortex
PubMed: 37198203
DOI: 10.1038/s41597-023-02214-y -
Neuron Aug 2023Hippocampal pyramidal cells represent an animal's position in space together with specific contexts and events. However, it is largely unknown how distinct types of...
Hippocampal pyramidal cells represent an animal's position in space together with specific contexts and events. However, it is largely unknown how distinct types of GABAergic interneurons contribute to such computations. We recorded from the intermediate CA1 hippocampus of head-fixed mice exhibiting odor-to-place memory associations during navigation in a virtual reality (VR). The presence of an odor cue and its prediction of a different reward location induced a remapping of place cell activity in the virtual maze. Based on this, we performed extracellular recording and juxtacellular labeling of identified interneurons during task performance. The activity of parvalbumin (PV)-expressing basket, but not of PV-expressing bistratified cells, reflected the expected contextual change in the working-memory-related sections of the maze. Some interneurons, including identified cholecystokinin-expressing cells, decreased activity during visuospatial navigation and increased activity during reward. Our findings suggest that distinct types of GABAergic interneuron are differentially involved in cognitive processes of the hippocampus.
Topics: Rats; Mice; Animals; Rats, Sprague-Dawley; Odorants; Spatial Navigation; Interneurons; Hippocampus; Pyramidal Cells; Parvalbumins
PubMed: 37279749
DOI: 10.1016/j.neuron.2023.05.007 -
ENeuro 2022Parvalbumin (PV)-producing neurons are the largest subpopulation of cortical GABAergic interneurons, which mediate lateral, feedforward, and feedback inhibition in local...
Parvalbumin (PV)-producing neurons are the largest subpopulation of cortical GABAergic interneurons, which mediate lateral, feedforward, and feedback inhibition in local circuits and modulate the activity of pyramidal neurons. Clarifying the specific connectivity between pyramidal and PV neurons is essential for understanding the role of PV neurons in local circuits. In the present study, we visualized somas and dendrites of PV neurons using transgenic mice in which PV neurons specifically express membrane-targeted GFP, and intracellularly labeled local axons of 26 pyramidal neurons in layers 2-6 in acute slices of the motor-associated cortex from transgenic mice. We mapped morphologically distribution of inputs from a pyramidal neuron to PV neurons based on contact sites (appositions) between the axons from an intracellularly filled pyramidal neuron and the dendrites of PV neurons. Layer 6 corticothalamic (CT)-like pyramidal neurons formed appositions to PV neurons at a significantly higher rate than other pyramidal neurons. The percentage of apposed varicosities to all the labeled varicosities of layer 6 CT-like neurons was 28%, and that of the other pyramidal neurons was 12-19%. Layer 6 CT-like neurons preferentially formed appositions with PV neurons in layers 5b-6, while other pyramidal neurons uniformly formed appositions with PV neurons in all layers. Furthermore, both layer 6 CT-like and corticocortical-like neurons more frequently formed compound appositions, where two or more appositions were located on a dendritic branch, than other pyramidal neurons. Layer 6 CT neurons may contribute to intracortical information processing through preferential connections with PV neurons in layers 5b-6.
Topics: Animals; Dendrites; Interneurons; Mice; Mice, Transgenic; Parvalbumins; Pyramidal Cells
PubMed: 34965927
DOI: 10.1523/ENEURO.0567-20.2021