scholarly journals Time-Dependent Recruitment of Prelimbic Prefrontal Circuits for Retrieval of Fear Memory

2021 ◽  
Vol 15 ◽  
Author(s):  
Kelvin Quiñones-Laracuente ◽  
Alexis Vega-Medina ◽  
Gregory J. Quirk

The long-lasting nature of fear memories is essential for survival, but the neural circuitry for retrieval of these associations changes with the passage of time. We previously reported a time-dependent shift from prefrontal-amygdalar circuits to prefrontal-thalamic circuits for the retrieval of auditory fear conditioning. However, little is known about the time-dependent changes in the originating site, the prefrontal cortex. Here we monitored the responses of prelimbic (PL) prefrontal neurons to conditioned tones at early (2 h) vs. late (4 days) timepoints following training. Using c-Fos, we find that PL neurons projecting to the amygdala are activated early after learning, but not later, whereas PL neurons projecting to the paraventricular thalamus (PVT) show the opposite pattern. Using unit recording, we find that PL neurons in layer V (the origin of projections to amygdala) showed cue-induced excitation at earlier but not later timepoints, whereas PL neurons in Layer VI (the origin of projections to PVT) showed cue-induced inhibition at later, but not earlier, timepoints, along with an increase in spontaneous firing rate. Thus, soon after conditioning, there are conditioned excitatory responses in PL layer V which influence the amygdala. With the passage of time, however, retrieval of fear memories shifts to inhibitory responses in PL layer VI which influence the midline thalamus.

2022 ◽  
Vol 13 ◽  
Author(s):  
Francisco Javier Fuentealba-Villarroel ◽  
Josué Renner ◽  
Arlete Hilbig ◽  
Oliver J. Bruton ◽  
Alberto A. Rasia-Filho

The human posteromedial cortex (PMC), which includes the precuneus (PC), represents a multimodal brain area implicated in emotion, conscious awareness, spatial cognition, and social behavior. Here, we describe the presence of Nissl-stained elongated spindle-shaped neurons (suggestive of von Economo neurons, VENs) in the cortical layer V of the anterior and central PC of adult humans. The adapted “single-section” Golgi method for postmortem tissue was used to study these neurons close to pyramidal ones in layer V until merging with layer VI polymorphic cells. From three-dimensional (3D) reconstructed images, we describe the cell body, two main longitudinally oriented ascending and descending dendrites as well as the occurrence of spines from proximal to distal segments. The primary dendritic shafts give rise to thin collateral branches with a radial orientation, and pleomorphic spines were observed with a sparse to moderate density along the dendritic length. Other spindle-shaped cells were observed with straight dendritic shafts and rare branches or with an axon emerging from the soma. We discuss the morphology of these cells and those considered VENs in cortical areas forming integrated brain networks for higher-order activities. The presence of spindle-shaped neurons and the current discussion on the morphology of putative VENs address the need for an in-depth neurochemical and transcriptomic characterization of the PC cytoarchitecture. These findings would include these spindle-shaped cells in the synaptic and information processing by the default mode network and for general intelligence in healthy individuals and in neuropsychiatric disorders involving the PC in the context of the PMC functioning.


2009 ◽  
Vol 101 (2) ◽  
pp. 641-654 ◽  
Author(s):  
Sofija Andjelic ◽  
Thierry Gallopin ◽  
Bruno Cauli ◽  
Elisa L. Hill ◽  
Lisa Roux ◽  
...  

The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity.


2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Sara Sabuee ◽  
S. Mohammad Ahmadi-Soleimani ◽  
Hossein Azizi

Abstract Introduction Adolescence is a critical period in brain development, and it is characterized by persistent maturational alterations in the function of central nervous system. In this respect, many studies show the non-medical use of opioid drugs by adolescents. Although this issue has rather widely been addressed during the last decade, cellular mechanisms through which adolescent opioid exposure may induce long-lasting effects are not duly understood. The present study examined the effect of adolescent morphine exposure on neuronal responses of lateral paragigantocellularis nucleus to naloxone in adult morphine-dependent rats. Methods Adolescent male Wistar rats (31 days old) received increasing doses of morphine (from 2.5 to 25 mg/kg, twice daily, s.c.) for 10 days. Control subjects were injected saline with the same protocol. After a drug-free interval (20 days), animals were rendered dependent on morphine during 10 days (10 mg/kg, s.c., twice daily). Then, extracellular single-unit recording was performed to investigate neural response of LPGi to naloxone in adult morphine-dependent rats. Results Results indicated that adolescent morphine treatment increases the number of excitatory responses to naloxone, enhances the baseline activity and alters the pattern of firing in neurons with excitatory responses in adult morphine-dependent rats. Moreover, the intensity of excitatory responses is reduced following the early life drug intake. Conclusion It seems that prolonged opioid exposure during adolescence induces long-lasting neurobiological changes in LPGi responsiveness to future opioid withdrawal challenges.


2017 ◽  
Author(s):  
Yevgenij Yanovsky ◽  
Jurij Brankačk

summaryThe relative electrical conductivity gradient with depth was estimated in the frontal cortex of anaesthetized rats. Current source density (CSD) approximations of field potentials evoked by ventromedial thalamic stimulations with an assumed homogeneous electrical conductivity of the neocortical tissue were compared to those with correction for the estimated conductivity gradient. In spite of the cellular heterogeneity the electrical conductivity of the frontal cortical tissue was found to be fairly homogeneous inside the superficial (layers I through IV) or deep layers (V- VI). The relative conductivity increased twofold at the transition between superficial and deep layers. Regardless of this changes CSD analysis of the field potentials evoked by ventromedial thalamic stimulation revealed negligible differences between estimations ignoring the conductivity and those taking the conductivity into account. No sinks or sources appeared or disappeared. Both CSD approximations revealed: 1) a strong sink in layer I representing most likely summed monosynaptic EPSPs of the ventromedial thalamic afferents; 2) a strong sink in layer VI, probably representing summed disynaptic EPSPs on dendrites of layer VI pyramidal cells, generated by axons of upper layer pyramidal cells; and 3) a sink in lower layer V representing probably threesynaptic summed EPSPs on dendrites of layer V pyramidal cells.


2019 ◽  
Author(s):  
Liang Li ◽  
Yajie Tang ◽  
Leqiang Sun ◽  
Jinsong Yu ◽  
Hui Gong ◽  
...  

AbstractThe elegant functions of the brain are facilitated by sophisticated connections between neurons, the architecture of which is frequently characterized by one nucleus connecting to multiple targets via projection neurons. Delineating the sub-nucleus fine architecture of projection neurons in a certain nucleus could greatly facilitate its circuit, computational, and functional resolution. Here, we developed multi-fluorescent rabies virus to delineate the fine organization of corticothalamic projection neuron subsets in the primary visual cortex (V1). By simultaneously labeling multiple distinct subsets of corticothalamic projection neurons in V1 from their target nuclei in thalamus (dLGN, LP, LD), we observed that V1-dLGN corticothalamic neurons were densely concentrated in layer VI, except for several sparsely scattered neurons in layer V, while V1-LP and V1-LD corticothalamic neurons were localized to both layers V and VI. Meanwhile, we observed a fraction of V1 corticothalamic neurons targeting multiple thalamic nuclei, which was further confirmed by fMOST whole-brain imaging. We further conceptually proposed an upgraded sub-nucleus tracing system with higher throughput (21 subsets) for more complex architectural tracing. The multi-fluorescent RV tracing tool can be extensively applied to resolve architecture of projection neuron subsets, with a strong potential to delineate the computational and functional organization of these nuclei.


1988 ◽  
Vol 60 (2) ◽  
pp. 798-828 ◽  
Author(s):  
J. Kruger ◽  
F. Aiple

1. In the infragranular layers of the striate cortex of three monkeys, we studied tangential neuronal interactions by analyzing cross-correlograms calculated from spike trains recorded with 30 closely spaced microelectrodes. 2. There are two major types of correlogram structures--"narrow" peaks a few milliseconds wide, sometimes accompanied by small lateral troughs, and "broad" peaks approximately 30- to 100-ms wide. Isolated troughs are rare. Both types of structures are superimposed in the same correlograms; they are not due to shared optical stimulation. 3. In layer VI, narrow peaks are largest in a short lateral range of approximately 220 micron, and they depend on ocularity. In layer V, the lateral range is greater, and the dependency on ocularity is weak. 4. In addition, narrow peaks are largest at distances of 160 micron if the angles of preferred orientation are similar. In layer VI, however, at tangential distances of 300-400 micron, peaks are smaller, and troughs are found more often, for neuron pairs with parallel orientations compared with those with orthogonal orientations. From the agreement of this finding with a cooperative theory, we conclude that orientation selectivity is shaped by collective interactions. 5. Broad peaks always depend on ocularity, and the associated lateral interaction range exceeds the maximum of 1 mm investigated. Their size sharply decreases with receptive-field distance. 6. Average mutual delays of spikes of neuron pairs, manifest as lateral displacements of broad peaks, are interdependent; the delay between neurons 1 and 3 is the sum of that of neurons 1 and 2 and of neurons 2 and 3. This feature permits to rank the neurons on a "delay scale." 7. We conclude from 5 and 6 above that broad peaks partly result from intraretinal interactions whose effects are transmitted to the cortex via slow and fast pathways. 8. Lateral troughs adjacent to narrow peaks provide evidence that neurons at the "slow" end of the delay scale inhibit those at the "fast" end, and to a lesser extent, nondirectional neurons inhibit directional ones.


2019 ◽  
Vol 317 (4) ◽  
pp. C800-C812 ◽  
Author(s):  
Ying Wang ◽  
An-Qi Chen ◽  
Yan Xue ◽  
Mei-Fang Liu ◽  
Cui Liu ◽  
...  

Orexin is a peptide neurotransmitter released in the globus pallidus. Morphological evidence reveals that both orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) exist in the globus pallidus. Here we showed that bilateral microinjection of both orexin-A and orexin-B into the globus pallidus alleviated motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Further in vivo extracellular single-unit recording revealed that the basal spontaneous firing rate of the globus pallidus neurons in MPTP parkinsonian mice was slower than that of normal mice. Application of orexin-A or orexin-B significantly increased the spontaneous firing rate of pallidal neurons. The influx of Ca2+ through the L-type Ca2+ channel is the major mechanism involved in orexin-induced excitation in the globus pallidus. Orexin-A-induced increase in firing rate of pallidal neurons in MPTP parkinsonian mice was stronger than that of normal mice. Orexin-A exerted both electrophysiological and behavioral effects mainly via OX1R, and orexin-B exerted the effects via OX2R. Endogenous orexins modulated the excitability of globus pallidus neurons mainly through OX1R. The present behavioral and electrophysiological results suggest that orexins ameliorate parkinsonian motor deficits through increasing the spontaneous firing of globus pallidus neurons.


2008 ◽  
Vol 99 (2) ◽  
pp. 950-957 ◽  
Author(s):  
Yoshifumi Ueta ◽  
Ryo Yamamoto ◽  
Shigeki Sugiura ◽  
Kaoru Inokuchi ◽  
Nobuo Kato

Homer1a/Vesl-1S is an activity-dependently induced member of the scaffold protein family Homer/Vesl, which is known to link group I metabotropic glutamate receptors (mGluRs) to endoplasmic calcium release channels and to regulate them. Here we studied roles of Homer 1a in inducing long-term depression (LTD) in rat visual cortex slices. Homer 1a protein was injected by diffusion from whole cell patch pipettes. In layer VI pyramidal cells, LTD was reduced in magnitude with Homer 1a. LTD in layer VI was suppressed by applying antagonists of mGluR5, a subtype of group I mGluRs expressed with higher density than mGluR1 in neocortex pyramidal cells, or inositol-1,4,5-triphosphate receptors (IP3Rs) but not that against N-methyl-d-aspartate receptors (NMDARs). In layer II/III or layer V, Homer 1a injection was unable to affect LTD, which is mostly dependent on NMDARs and not on group I mGluRs in these layers. To examine the effects of endogenous Homer 1a, electroconvulsive shock (ECS) was applied. Homer 1a thereby induced, as did Homer 1a injection, reduced LTD magnitude in layer VI pyramidal cells and failed to do so in layer II/III or layer V pyramidal cells. These results indicate that both exo- and endogenous Homer 1a suppressed LTD in a cortical layer-specific manner, and its layer-specificity may be explained by the high affinity of Homer 1a to group I mGluRs.


1994 ◽  
Vol 72 (2) ◽  
pp. 578-591 ◽  
Author(s):  
Y. Kang ◽  
F. Kayano

1. Intracellular recordings were made from layer VI pyramidal cells in in vitro slice preparations of the cat motor cortex (area 4 gamma). Layer VI pyramidal cells were identified morphologically by intracellular injection of biocytin. 2. Of 22 layer VI pyramidal cells examined, single action potentials were followed by depolarizing afterpotentials (DAP) in 9 cells, but were not followed by DAP in the remaining 13 cells. The amplitude of DAP was 3.4 +/- 1.4 mV (mean +/- SD, n = 9) when measured from the negative peak of fast afterhyperpolarization to the peak of DAP. 3. In response to depolarizing current pulses with a duration of 300–400 ms, pyramidal cells showing DAP displayed a train of action potentials in a phasic-tonic pattern without any appreciable adaptation in the tonic firing, whereas pyramidal cells lacking DAP exhibited a weak adaptation after phasic firing. Anomalous rectification was seen in both pyramidal cells showing DAP and those lacking DAP. 4. Repetitive doublet or triplet spiking was induced in DAP-showing pyramidal cells in response to a depolarizing current pulse after injecting strong depolarizing current pulses of 400 ms duration at 1 Hz for 30–60 s, but was never induced in DAP-lacking pyramidal cells. Doublet/triplet spiking lasted 5–10 min and returned to the original single spiking. An application of CsCl induced a burst firing in DAP-showing pyramidal cells. 5. In the nine pyramidal cells showing DAP, seven cells had shorter apical dendrites that arborized extensively at layer V and terminated in the middle part of layer III. In the 13 pyramidal cells lacking DAP, 11 cells had longer apical dendrites that arborized less frequently and extended into layer II or I. Main axons could be traced into the deep white matter in 17 of the 22 layer VI pyramidal cells examined. 6. Ascending recurrent axon collaterals were more prominent in pyramidal cells with longer apical dendrites than in pyramidal cells with shorter apical dendrites. The terminal bouton-like swelling observed along the recurrent axon collaterals arising from the pyramidal cells with longer apical dendrite were distributed most densely at the level between the bottom part of layer III and the top part of layer V. In contrast, those arising from the pyramidal cells with shorter apical dendrite were distributed mainly at the levels of layers V and VI.(ABSTRACT TRUNCATED AT 400 WORDS)


2002 ◽  
Vol 357 (1428) ◽  
pp. 1659-1673 ◽  
Author(s):  
Edward G. Jones

The corticothalamic system has an important role in synchronizing the activities of thalamic and cortical neurons. Numerically, its synapses dominate the inputs to relay cells and to the γ–amino butyric acid (GABA)ergic cells of the reticular nucleus (RTN). The capacity of relay neurons to operate in different voltage–dependent functional modes determines that the inputs from the cortex have the capacity directly to excite the relay cells, or indirectly to inhibit them via the RTN, serving to synchronize high– or low–frequency oscillatory activity respectively in the thalamocorticothalamic network. Differences in the α–amino–3–hydroxy–5–methyl–4–isoxazolepropionic acid (AMPA) subunit composition of receptors at synapses formed by branches of the same corticothalamic axon in the RTN and dorsal thalamus are an important element in the capacity of the cortex to synchronize low–frequency oscillations in the network. Interactions of focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, with the specifically projecting core relay cells and diffusely projecting matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high–frequency oscillations that underlie discrete conscious events.


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