Functional and structural features of L2/3 pyramidal cells continuously covary with pial depth in mouse visual cortex

Pyramidal cells of neocortical layer 2/3 (L2/3 PyrCs) integrate signals from numerous brain areas and project throughout the neocortex. Within L2/3, PyrCs show functional and structural specializations depending on their pial depth, indicating participation in different functional microcircuits. However, it is unknown whether these depth-dependent differences result from separable L2/3 PyrC subtypes or whether functional and structural features represent a continuum while correlating with pial depth. Here, we assessed the stimulus selectivity, electrophysiological properties, dendritic morphology, and excitatory and inhibitory synaptic connectivity across the depth of L2/3 in the binocular visual cortex (bV1) of female mice. We find that the structure of the apical but not the basal dendritic tree varies with pial depth, which is accompanied by differences in passive but not active electrophysiological properties. PyrCs in lower L2/3 receive increased excitatory and inhibitory input from L4, while upper L2/3 PyrCs receive a larger proportion of intralaminar input. Complementary in vivo calcium imaging revealed a systematic change in visual responsiveness, with deeper L2/3 PyrCs showing more robust responses than superficial PyrCs. Furthermore, deeper L2/3 PyrCs are more strongly driven by contralateral than ipsilateral eye stimulation. In contrast, orientation- and direction-selectivity of L2/3 PyrCs are not dependent on pial depth. Importantly, the transitions of the various properties are gradual, and cluster analysis does not support the classification of L2/3 PyrCs into discrete subtypes. These results show that L2/3 PyrCs' multiple functional and structural properties systematically correlate with their depth within L2/3, forming a continuum rather than representing discrete subtypes.

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Relationship between input connectivity, morphology and orientation tuning of layer 2/3 pyramidal cells in mouse visual cortex

10.1101/2020.06.03.127191 ◽

2020 ◽

Cited By ~ 1

Author(s):

Simon Weiler ◽

Drago Guggiana Nilo ◽

Tobias Bonhoeffer ◽

Mark Hübener ◽

Tobias Rose ◽

...

Keyword(s):

Visual Cortex ◽

Synaptic Input ◽

Pyramidal Cells ◽

Excitatory Input ◽

Orientation Tuning ◽

Inhibitory Input ◽

Layer 2 ◽

Dendritic Complexity ◽

Inhibitory Synaptic Input

AbstractNeocortical pyramidal cells (PCs) display functional specializations defined by their excitatory and inhibitory circuit connectivity. For layer 2/3 (L2/3) PCs, little is known about the detailed relationship between their neuronal response properties, dendritic structure and their underlying circuit connectivity at the level of single cells. Here, we ask whether L2/3 PCs in mouse primary visual cortex (V1) differ in their functional intra- and interlaminar connectivity patterns, and how this relates to differences in visual response properties. Using a combined approach, we first characterized the orientation and direction tuning of individual L2/3 PCs with in vivo 2-photon calcium imaging. Subsequently, we performed excitatory and inhibitory synaptic input mapping of the same L2/3 PCs in brain slices using laser scanning photostimulation (LSPS).Our data from this structure-connectivity-function analysis show that the sources of excitatory and inhibitory synaptic input are different in their laminar origin and horizontal location with respect to cell position: On average, L2/3 PCs receive more inhibition than excitation from within L2/3, whereas excitation dominates input from L4 and L5. Horizontally, inhibitory input originates from locations closer to the horizontal position of the soma, while excitatory input arises from more distant locations in L4 and L5. In L2/3, the excitatory and inhibitory inputs spatially overlap on average. Importantly, at the level of individual neurons, PCs receive inputs from presynaptic cells located spatially offset, vertically and horizontally, relative to the soma. These input offsets show a systematic correlation with the preferred orientation of the postsynaptic L2/3 PC in vivo. Unexpectedly, this correlation is higher for inhibitory input offsets within L2/3 than for excitatory input offsets. When relating the dendritic complexity of L2/3 PCs to their orientation tuning, we find that sharply tuned cells have a less complex apical tree compared to broadly tuned cells. These results indicate that the spatial input offsets of the functional input connectivity are linked to orientation preference, while the orientation selectivity of L2/3 PCs is more related to the dendritic complexity.

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Neuronal gain modulability is determined by dendritic morphology: a computational optogenetic study

10.1101/096586 ◽

2016 ◽

Author(s):

Sarah Jarvis ◽

Konstantin Nikolic ◽

Simon R Schultz

Keyword(s):

Dendritic Tree ◽

Gain Control ◽

Pyramidal Cells ◽

Dendritic Morphology ◽

Inhibitory Input ◽

List Type ◽

Moderate Degree ◽

Gain Modulation ◽

Input Output

AbstractThe mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable. To investigate how different topologies of the neuronal dendritic tree affect the neuron’s input-output characteristics we generate branching geometries which replicate morphological features of most common neurons, but keep the number of branches and overall area of dendrites approximately constant. We found a relationship between a neuron’s gain modulability and its dendritic morphology, with neurons with bipolar dendrites with a moderate degree of branching being most receptive to control of the gain of their input-output relationship. The theory was then tested and confirmed on two examples of realistic neurons: 1) layer V pyramidal cells - confirming their role in neural circuits as a regulator of the gain in the circuit in addition to acting as the primary excitatory neurons, and 2) stellate cells. In addition to providing testable predictions and a novel application of dual-opsins, our model suggests that innervation of all dendritic subdomains is required for full gain modulation, revealing the importance of dendritic targeting in the generation of neuronal gain control and the functions that it subserves. Finally, our study also demonstrates that neurophysiological investigations which use direct current injection into the soma and bypass the dendrites may miss some important neuronal functions, such as gain modulation.Author SummaryGain modulability indicated by dendritic morphologyPyramidal cell-like shapes optimally receptive to modulationAll dendritic subdomains required for gain modulation, partial illumination is insufficientComputational optogenetic models improve and refine experimental protocols

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Temporo-nasally biased moving grating selectivity in mouse primary visual cortex

10.1101/708644 ◽

2019 ◽

Author(s):

Marie Tolkiehn ◽

Simon R. Schultz

Keyword(s):

Visual Cortex ◽

Spatial Frequency ◽

Primary Visual Cortex ◽

Moving Objects ◽

Direction Selectivity ◽

Orientation Tuning ◽

High Signal ◽

Forward Movement ◽

Upward Moving

AbstractOrientation tuning in mouse primary visual cortex (V1) has long been reported to have a random or “salt-and-pepper” organisation, lacking the structure found in cats and primates. Laminar in-vivo multi-electrode array recordings here reveal previously elusive structure in the representation of visual patterns in the mouse visual cortex, with temporo-nasally drifting gratings eliciting consistently highest neuronal responses across cortical layers and columns, whilst upward moving gratings reliably evoked the lowest activities. We suggest this bias in direction selectivity to be behaviourally relevant as objects moving into the visual field from the side or behind may pose a predatory threat to the mouse whereas upward moving objects do not. We found furthermore that direction preference and selectivity was affected by stimulus spatial frequency, and that spatial and directional tuning curves showed high signal correlations decreasing with distance between recording sites. In addition, we show that despite this bias in direction selectivity, it is possible to decode stimulus identity and that spatiotemporal features achieve higher accuracy in the decoding task whereas spike count or population counts are sufficient to decode spatial frequencies implying different encoding strategies.Significance statementWe show that temporo-nasally drifting gratings (i.e. opposite the normal visual flow during forward movement) reliably elicit the highest neural activity in mouse primary visual cortex, whereas upward moving gratings reliably evoke the lowest responses. This encoding may be highly behaviourally relevant, as objects approaching from the periphery may pose a threat (e.g. predators), whereas upward moving objects do not. This is a result at odds with the belief that mouse primary visual cortex is randomly organised. Further to this biased representation, we show that direction tuning depends on the underlying spatial frequency and that tuning preference is spatially correlated both across layers and columns and decreases with cortical distance, providing evidence for structural organisation in mouse primary visual cortex.

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A neural circuit for gamma-band coherence across the retinotopic map in mouse visual cortex

eLife ◽

10.7554/elife.28569 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 13

Author(s):

Richard Hakim ◽

Kiarash Shamardani ◽

Hillel Adesnik

Keyword(s):

Visual Cortex ◽

Neural Circuit ◽

Brain Slices ◽

Pyramidal Cells ◽

Gamma Oscillations ◽

Gamma Band ◽

Neuron Activity ◽

Mouse Visual Cortex ◽

Retinotopic Map

Cortical gamma oscillations have been implicated in a variety of cognitive, behavioral, and circuit-level phenomena. However, the circuit mechanisms of gamma-band generation and synchronization across cortical space remain uncertain. Using optogenetic patterned illumination in acute brain slices of mouse visual cortex, we define a circuit composed of layer 2/3 (L2/3) pyramidal cells and somatostatin (SOM) interneurons that phase-locks ensembles across the retinotopic map. The network oscillations generated here emerge from non-periodic stimuli, and are stimulus size-dependent, coherent across cortical space, narrow band (30 Hz), and depend on SOM neuron but not parvalbumin (PV) neuron activity; similar to visually induced gamma oscillations observed in vivo. Gamma oscillations generated in separate cortical locations exhibited high coherence as far apart as 850 μm, and lateral gamma entrainment depended on SOM neuron activity. These data identify a circuit that is sufficient to mediate long-range gamma-band coherence in the primary visual cortex.

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Electrophysiological Diversity of Layer 5 Pyramidal Cells in the Prefrontal Cortex of the Rhesus Monkey: In Vitro Slice Studies

Journal of Neurophysiology ◽

10.1152/jn.00585.2007 ◽

2007 ◽

Vol 98 (5) ◽

pp. 2622-2632 ◽

Cited By ~ 34

Author(s):

Yu-Ming Chang ◽

Jennifer I. Luebke

Keyword(s):

Prefrontal Cortex ◽

Rhesus Monkey ◽

Spike Train ◽

Pyramidal Cells ◽

Cell Types ◽

Dendritic Morphology ◽

Firing Patterns ◽

Electrophysiological Properties ◽

Whole Cell Patch Clamp

Whole cell patch-clamp recordings were employed to characterize the electrophysiological properties of layer 5 pyramidal cells in slices of the prefrontal cortex (Area 46) of the rhesus monkey. Four electrophysiologically distinct cell types were discriminated based on distinctive repetitive action potential (AP) firing patterns and single AP characteristics: regular-spiking slowly adapting type-1 cells (RS1; 62%), regular-spiking slowly adapting type-2 cells (RS2; 18%), regular-spiking fast-adapting cells (FA; 15%), and intrinsically bursting cells (IB; 5%). These cells did not differ with regard to their location in layer 5 nor in their dendritic morphology. In RS1 cells, AP threshold and amplitude did not change significantly during a 2-s spike train, whereas in RS2 and FA cells, AP threshold increased significantly and AP amplitude decreased significantly during the train. In FA cells, complete adaptation of AP firing was observed within 600 ms. IB cells displayed an all-or-none burst of three to six APs, followed by RS1-type firing behavior. RS1 cells could be further subdivided into three subtypes. Low-threshold spiking (LTS) RS1 cells exhibited an initial doublet riding on a depolarizing potential at the onset of a spike train and a prominent depolarizing afterpotential (DAP); intermediate RS1 cells (IM) exhibited a DAP, but no initial doublet, and non-LTS RS1 cells exhibited neither a DAP nor an initial doublet. RS2 and FA cells did not exhibit a DAP or initial doublets. The distinctive firing patterns of these diverse layer 5 pyramidal cells may reflect different roles played by these cells in the mediation of subcortical neuronal activity by the dorsolateral PFC.

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GABAergic interneurons excite neonatal hippocampus in vivo

Science Advances ◽

10.1126/sciadv.aba1430 ◽

2020 ◽

Vol 6 (24) ◽

pp. eaba1430 ◽

Cited By ~ 5

Author(s):

Yasunobu Murata ◽

Matthew T. Colonnese

Keyword(s):

Visual Cortex ◽

Synapse Formation ◽

Reversal Potential ◽

Pyramidal Cells ◽

Gabaergic Neurons ◽

Network Activity ◽

Gabaergic Interneuron ◽

Gabaergic Interneurons ◽

Early Postnatal Development

GABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are excitatory in CA1 hippocampus at postnatal day 3 (P3) and are responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas visual cortex interneurons are already inhibitory by P3 and remain so throughout development. These regional and age-specific differences are the result of a change in chloride reversal potential, because direct activation of light-gated anion channels in glutamatergic neurons drives CA1 firing at P3, but silences it at P7 in CA1, and at all ages in visual cortex. This study in the intact brain reveals that GABAergic interneuron excitation is essential for network activity in neonatal hippocampus and confirms that visual cortical interneurons are inhibitory throughout early postnatal development.

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Cellular mechanisms for response heterogeneity among L2/3 pyramidal cells in whisker somatosensory cortex

Journal of Neurophysiology ◽

10.1152/jn.00848.2013 ◽

2014 ◽

Vol 112 (2) ◽

pp. 233-248 ◽

Cited By ~ 15

Author(s):

Justin Elstrott ◽

Kelly B. Clancy ◽

Haani Jafri ◽

Igor Akimenko ◽

Daniel E. Feldman

Keyword(s):

Somatosensory Cortex ◽

Pyramidal Cells ◽

Dendritic Morphology ◽

Membrane Properties ◽

Intrinsic Excitability ◽

High Threshold ◽

Cellular Mechanisms ◽

Inhibitory Conductance

Whisker deflection evokes sparse, low-probability spiking among L2/3 pyramidal cells in rodent somatosensory cortex (S1), with spiking distributed nonuniformly between more and less responsive cells. The cellular and local circuit factors that determine whisker responsiveness across neurons are unclear. To identify these factors, we used two-photon calcium imaging and loose-seal recording to identify more and less responsive L2/3 neurons in S1 slices in vitro, during feedforward recruitment of the L2/3 network by L4 stimulation. We observed a broad gradient of spike recruitment thresholds within local L2/3 populations, with low- and high-threshold cells intermixed. This recruitment gradient was significantly correlated across different L4 stimulation sites, and between L4-evoked and whisker-evoked responses in vivo, indicating that a substantial component of responsiveness is independent of tuning to specific feedforward inputs. Low- and high-threshold L2/3 pyramidal cells differed in L4-evoked excitatory synaptic conductance and intrinsic excitability, including spike threshold and the likelihood of doublet spike bursts. A gradient of intrinsic excitability was observed across neurons. Cells that spiked most readily to L4 stimulation received the most synaptic excitation but had the lowest intrinsic excitability. Low- and high-threshold cells did not differ in dendritic morphology, passive membrane properties, or L4-evoked inhibitory conductance. Thus multiple gradients of physiological properties exist across L2/3 pyramidal cells, with excitatory synaptic input strength best predicting overall spiking responsiveness during network recruitment.

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Direction selectivity in a model of the starburst amacrine cell

Visual Neuroscience ◽

10.1017/s0952523804214109 ◽

2004 ◽

Vol 21 (4) ◽

pp. 611-625 ◽

Cited By ~ 54

Author(s):

JOHN J. TUKKER ◽

W. ROWLAND TAYLOR ◽

ROBERT G. SMITH

Keyword(s):

Amacrine Cell ◽

Dendritic Tree ◽

Sine Wave ◽

Direction Selectivity ◽

Membrane Properties ◽

Calcium Signal ◽

Inhibitory Input ◽

Excitatory Postsynaptic Potential ◽

Global Signal ◽

Starburst Amacrine Cell

The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to provide the directional inhibitory input recorded in On–Off direction-selective ganglion cells (DSGCs). While voltage recordings from the somas of SBACs have not shown robust direction selectivity (DS), the dendritic tips of these cells display direction-selective calcium signals, even when γ-aminobutyric acid (GABAa,c) channels are blocked, implying that inhibition is not necessary to generate DS. This suggested that the distinctive morphology of the SBAC could generate a DS signal at the dendritic tips, where most of its synaptic output is located. To explore this possibility, we constructed a compartmental model incorporating realistic morphological structure, passive membrane properties, and excitatory inputs. We found robust DS at the dendritic tips but not at the soma. Two-spot apparent motion and annulus radial motion produced weak DS, but thin bars produced robust DS. For these stimuli, DS was caused by the interaction of a local synaptic input signal with a temporally delayed “global” signal, that is, an excitatory postsynaptic potential (EPSP) that spread from the activated inputs into the soma and throughout the dendritic tree. In the preferred direction the signals in the dendritic tips coincided, allowing summation, whereas in the null direction the local signal preceded the global signal, preventing summation. Sine-wave grating stimuli produced the greatest amount of DS, especially at high velocities and low spatial frequencies. The sine-wave DS responses could be accounted for by a simple mathematical model, which summed phase-shifted signals from soma and dendritic tip. By testing different artificial morphologies, we discovered DS was relatively independent of the morphological details, but depended on having a sufficient number of inputs at the distal tips and a limited electrotonic isolation. Adding voltage-gated calcium channels to the model showed that their threshold effect can amplify DS in the intracellular calcium signal.

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Functional Properties of Fast Spiking Interneurons and Their Synaptic Connections With Pyramidal Cells in Primate Dorsolateral Prefrontal Cortex

Journal of Neurophysiology ◽

10.1152/jn.00787.2004 ◽

2005 ◽

Vol 93 (2) ◽

pp. 942-953 ◽

Cited By ~ 91

Author(s):

Guillermo González-Burgos ◽

Leonid S. Krimer ◽

Nadya V. Povysheva ◽

German Barrionuevo ◽

David A. Lewis

Keyword(s):

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Pyramidal Cells ◽

Synaptic Connections ◽

Electrophysiological Properties ◽

Axonal Arborization ◽

Presynaptic Mechanisms ◽

Dorsolateral Prefrontal ◽

Fast Spiking

Recent studies suggest that fast-spiking (FS) interneurons of the monkey dorsolateral prefrontal cortex (DLPFC) exhibit task-related firing during working-memory tasks. To gain further understanding of the functional role of FS neurons in monkey DLPFC, we described the in vitro electrophysiological properties of FS interneurons and their synaptic connections with pyramidal cells in layers 2/3 of areas 9 and 46. Extracellular spike duration was found to distinguish FS cells from non-FS interneuron subtypes. However, a substantial overlap in extracellular spike duration between these populations would make classification of individual interneurons difficult. FS neurons could be divided into two main morphological groups, chandelier and basket neurons, with very similar electrophysiological properties but significantly different horizontal spread of the axonal arborization. In paired cell recordings, unitary inhibitory postsynaptic potentials (IPSPs) elicited by FS neurons in pyramidal cells had rapid time course, small amplitude at resting membrane potential, and were mediated by GABAA receptors. Repetitive FS neuron stimulation, partially mimicking the sustained firing of interneurons in vivo, produced short-term depression of the unitary IPSPs, present at connections made by both basket and chandelier neurons and due at least in part to presynaptic mechanisms. These results suggest that FS neurons and their synaptic connections with pyramidal cells have homogeneous physiological properties. Thus different functional roles of basket and chandelier neurons in the DLPFC in vivo must arise from the distinct properties of the interneuronal axonal arborization or from a different functional pattern of excitatory and inhibitory connections with other components of the DLPFC neuronal network.

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The role of ipsilateral and contralateral inputs from primary cortex in responses of area 21a neurons in cats

Visual Neuroscience ◽

10.1017/s0952523800003801 ◽

1994 ◽

Vol 11 (5) ◽

pp. 839-849 ◽

Cited By ~ 7

Author(s):

A. Michalski ◽

B. M. Wimborne ◽

G. H. Henry

Keyword(s):

Visual Cortex ◽

Primary Visual Cortex ◽

Tuning Curve ◽

Excitatory Input ◽

Direction Selectivity ◽

Orientation Tuning ◽

Inhibitory Input ◽

Area 21A ◽

Areas 17 And 18 ◽

Orientation Specificity

AbstractNeuronal responses in cat visual area 21a were analyzed when the primary visual cortex (areas 17 and 18) was deactivated by cooling. Ipsilateral and contralateral cortices were deactivated separately. Results established that (1) cooling the ipsilateral primary cortex diminished the activity of all area 21a cells and, in 30%, blocked responsiveness altogether, and (2) cooling the contralateral primary cortex initially increased activity in area 21a cells but, with further cooling, reduced it to below the original level although only 9% of cells ceased responding. These findings were then compared to earlier results in which bilateral deactivation of the primary cortex greatly reduced and, in most cases, blocked the activity of area 21a cells (Michalski et al., 1993). Despite the response attenuation following cooling of the primary visual cortex (either ipsilateral or contralateral), neurons of area 21a retained their original orientation specificity and sharpness of tuning (measured as the half-width at half-height of the orientation tuning curve). Direction selectivity also tended to remain unchanged. We concluded that for area 21a cells (1) the ipsilateral primary cortex provides the main excitatory input; (2) the contralateral primary cortex supplies a large inhibitory input; and (3) the nature of orientation specificity, sharpness of orientation tuning, and direction selectivity are largely unaffected by removal of the ipsilateral hemisphere excitatory input or the contralateral hemisphere inhibitory input.

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