scholarly journals Conjunctive spatial and self-motion codes are topographically organized in the GABAergic cells of the lateral septum

PLoS Biology ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. e3001383
Author(s):  
Suzanne van der Veldt ◽  
Guillaume Etter ◽  
Coralie-Anne Mosser ◽  
Frédéric Manseau ◽  
Sylvain Williams
Keyword(s):  
Dorsal Hippocampus ◽  
Pyramidal Cells ◽  
Medial Septum ◽  
Excitatory Input ◽  
Lateral Septum ◽  
Neuronal Populations ◽  
Hippocampal Ca1 ◽  
Memory Network ◽  
Self Motion

The hippocampal spatial code’s relevance for downstream neuronal populations—particularly its major subcortical output the lateral septum (LS)—is still poorly understood. Here, using calcium imaging combined with unbiased analytical methods, we functionally characterized and compared the spatial tuning of LS GABAergic cells to those of dorsal CA3 and CA1 cells. We identified a significant number of LS cells that are modulated by place, speed, acceleration, and direction, as well as conjunctions of these properties, directly comparable to hippocampal CA1 and CA3 spatially modulated cells. Interestingly, Bayesian decoding of position based on LS spatial cells reflected the animal’s location as accurately as decoding using the activity of hippocampal pyramidal cells. A portion of LS cells showed stable spatial codes over the course of multiple days, potentially reflecting long-term episodic memory. The distributions of cells exhibiting these properties formed gradients along the anterior–posterior and dorsal–ventral axes of the LS, directly reflecting the topographical organization of hippocampal inputs to the LS. Finally, we show using transsynaptic tracing that LS neurons receiving CA3 and CA1 excitatory input send projections to the hypothalamus and medial septum, regions that are not targeted directly by principal cells of the dorsal hippocampus. Together, our findings demonstrate that the LS accurately and robustly represents spatial, directional as well as self-motion information and is uniquely positioned to relay this information from the hippocampus to its downstream regions, thus occupying a key position within a distributed spatial memory network.

scholarly journals Conjunctive spatial and idiothetic codes are topographically organized in the lateral septum

2020 ◽  
Author(s):  
Suzanne van der Veldt ◽  
Guillaume Etter ◽  
Fernanda Sosa ◽  
Coralie-Anne Mosser ◽  
Sylvain Williams
Keyword(s):  
Medial Septum ◽  
Place Cells ◽  
Lateral Septum ◽  
Head Direction ◽  
Neuronal Populations ◽  
Spatial Tuning ◽  
Hippocampal Ca1 ◽  
Memory Network ◽  
Anterior Posterior

AbstractThe relevance of the hippocampal spatial code for downstream neuronal populations – in particular its main subcortical output, the lateral septum (LS) - is still poorly understood. Here, we addressed this knowledge gap by first clarifying the organization of LS afferents and efferents via retrograde and anterograde trans-synaptic tracing. We found that mouse LS receives inputs from hippocampal subregions CA1, CA3, and subiculum, and in turn projects directly to the lateral hypothalamus (LH), ventral tegmental area (VTA), and medial septum (MS). Next, we functionally characterized the spatial tuning properties of LS GABAergic cells, the principal cells composing the LS, via calcium imaging combined with unbiased analytical methods. We identified a significant number of cells that are modulated by place (38.01%), speed (23.71%), acceleration (27.84%), and head-direction (23.09%), and conjunctions of these properties, with spatial tuning comparable to hippocampal CA1 and CA3 place cells. Bayesian decoding of position on the basis of LS place cells accurately reflected the location of the animal. The distributions of cells exhibiting these properties formed gradients along the anterior-posterior axis of the LS, directly reflecting the organization of hippocampal inputs to the LS. A portion of LS place cells showed stable fields over the course of multiple days, potentially reflecting long-term episodic memory. Together, our findings demonstrate that the LS accurately and robustly represents spatial and idiothetic information and is uniquely positioned to relay this information from the hippocampus to the VTA, LH, and MS, thus occupying a key position within this distributed spatial memory network.

scholarly journals The Entorhinal Cortical Alvear Pathway Differentially Excites Pyramidal Cells and Interneuron Subtypes in Hippocampal CA1

2020 ◽  
Author(s):  
Karen A Bell ◽  
Rayne Delong ◽  
Priyodarshan Goswamee ◽  
A Rory McQuiston
Keyword(s):  
Brain Slices ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Theta Burst Stimulation ◽  
Ca1 Pyramidal Cells ◽  
Whole Cell Patch Clamp ◽  
Hippocampal Ca1 ◽  
Physiological Impact ◽  
Theta Burst ◽  
Synaptic Responses

Abstract The entorhinal cortex alvear pathway is a major excitatory input to hippocampal CA1, yet nothing is known about its physiological impact. We investigated the alvear pathway projection and innervation of neurons in CA1 using optogenetics and whole cell patch clamp methods in transgenic mouse brain slices. Using this approach, we show that the medial entorhinal cortical alvear inputs onto CA1 pyramidal cells (PCs) and interneurons with cell bodies located in stratum oriens were monosynaptic, had low release probability, and were mediated by glutamate receptors. Optogenetic theta burst stimulation was unable to elicit suprathreshold activation of CA1 PCs but was capable of activating CA1 interneurons. However, different subtypes of interneurons were not equally affected. Higher burst action potential frequencies were observed in parvalbumin-expressing interneurons relative to vasoactive-intestinal peptide-expressing or a subset of oriens lacunosum-moleculare (O-LM) interneurons. Furthermore, alvear excitatory synaptic responses were observed in greater than 70% of PV and VIP interneurons and less than 20% of O-LM cells. Finally, greater than 50% of theta burst-driven inhibitory postsynaptic current amplitudes in CA1 PCs were inhibited by optogenetic suppression of PV interneurons. Therefore, our data suggest that the alvear pathway primarily affects hippocampal CA1 function through feedforward inhibition of select interneuron subtypes.

scholarly journals Long-term potentiation at single fiber inputs to hippocampal CA1 pyramidal cells.

1996 ◽  
Vol 93 (16) ◽  
pp. 8710-8715 ◽  
Author(s):  
J. T. Isaac ◽  
G. O. Hjelmstad ◽  
R. A. Nicoll ◽  
R. C. Malenka
Keyword(s):  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Single Fiber ◽  
Ca1 Pyramidal Cells ◽  
Term Potentiation ◽  
Hippocampal Ca1

Long-term study of dendritic spines from hippocampal CA1 pyramidal cells, after neuroprotective melatonin treatment following global cerebral ischemia in rats

2007 ◽  
Vol 423 (2) ◽  
pp. 162-166 ◽  
Author(s):  
Ignacio González-Burgos ◽  
Graciela Letechipía-Vallejo ◽  
Elisa López-Loeza ◽  
Gabriela Moralí ◽  
Miguel Cervantes
Keyword(s):  
Cerebral Ischemia ◽  
Dendritic Spines ◽  
Pyramidal Cells ◽  
Global Cerebral Ischemia ◽  
Melatonin Treatment ◽  
Term Study ◽  
Ca1 Pyramidal Cells ◽  
Long Term Study ◽  
Hippocampal Ca1

Intracellular Correlates of Spatial Memory Acquisition in Hippocampal Slices: Long-Term Disinhibition of CA1 Pyramidal Cells

2001 ◽  
Vol 86 (2) ◽  
pp. 881-899 ◽  
Author(s):  
Pavel A. Gusev ◽  
Daniel L. Alkon
Keyword(s):  
Dorsal Hippocampus ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Membrane Properties ◽  
Postsynaptic Potentials ◽  
Ca1 Pyramidal Cells ◽  
The Mean ◽  
Reversal Potentials

Despite many advances in our understanding of synaptic models of memory such as long-term potentiation and depression, cellular mechanisms that correlate with and may underlie behavioral learning and memory have not yet been conclusively determined. We used multiple intracellular recordings to study learning-specific modifications of intrinsic membrane and synaptic responses of the CA1 pyramidal cells (PCs) in slices of the rat dorsal hippocampus prepared at different stages of the Morris water maze (WM) task acquisition. Schaffer collateral stimulation evoked complex postsynaptic potentials (PSP) consisting of the excitatory and inhibitory postsynaptic potentials (EPSP and IPSP, respectively). After rats had learned the WM task, our major learning-specific findings included reduction of the mean peak amplitude of the IPSPs, delays in the mean peak latencies of the EPSPs and IPSPs, and correlation of the depolarizing-shifted IPSP reversal potentials and reduced IPSP-evoked membrane conductance. In addition, detailed isochronal analyses revealed that amplitudes of both early and late IPSP phases were reduced in a subset of the CA1 PCs after WM training was completed. These reduced IPSPs were significantly correlated with decreased IPSP conductance and with depolarizing-shifted IPSP reversal potentials. Input-output relations and initial rising slopes of the EPSP phase did not indicate learning-related facilitation as compared with the swim and naı̈ve controls. Another subset of WM-trained CA1 PCs had enhanced amplitudes of action potentials but no learning-specific synaptic changes. There were no WM training-specific modifications of other intrinsic membrane properties. These data suggest that long-term disinhibition in a subset of CA1 PCs may facilitate cell discharges that represent and record the spatial location of a hidden platform in a Morris WM.

Impairment of Hippocampal CA1 Heterosynaptic Transformation and Spatial Memory by β-Amyloid25–35

2002 ◽  
Vol 87 (5) ◽  
pp. 2441-2449 ◽  
Author(s):  
Miao-Kun Sun ◽  
Daniel L. Alkon
Keyword(s):  
Cognitive Impairment ◽  
Spatial Memory ◽  
Active Form ◽  
Pyramidal Cells ◽  
Single Pulse ◽  
Memory Impairments ◽  
Ca1 Pyramidal Cells ◽  
Synaptic Modification ◽  
Hippocampal Ca1

In Alzheimer's disease, the cholinergic damage (reduced neurotransmission) and cognitive impairment occur long before β-amyloid (Aβ) plaque formation. It has not been established whether the link between soluble Aβ and cholinergic functions contributes to synaptic dysfunction that underlies the cognitive impairment. Here, we report that Aβ25–35, an active form of Aβ, inhibited long-term synaptic modification that depends on the associative activation of cholinergic and GABAergic inputs when bilaterally injected intracerebroventricularly (icv; 200 μg/site). The Aβ microinjections did not affect single-pulse–evoked glutamatergic and GABAergic synaptic transmission onto the hippocampal CA1 pyramidal cells, while cholinergic intracellular θ was dramatically reduced by the Aβ25–35 injection. Spatial memory of the water maze task was also impaired by the bilateral icv Aβ25–35 injections, while bilateral microinjections of the same dose of Aβ35–25was ineffective in affecting the long-term synaptic modification evoked by associative activation of cholinergic and GABAergic inputs, the cholinergic intracellular θ, or producing memory impairments. Thus restoring the synaptic plasticity involved in this associative activation of cholinergic and GABAergic inputs may offer an important therapeutic target in the treatment of early Aβ-induced memory decline.

Altered Synaptic Dynamics and Hippocampal Excitability but Normal Long-Term Plasticity in Mice Lacking Hyperpolarizing GABAA Receptor-Mediated Inhibition in CA1 Pyramidal Neurons

2008 ◽  
Vol 99 (6) ◽  
pp. 3075-3089 ◽  
Author(s):  
Ruusu Riekki ◽  
Ivan Pavlov ◽  
Janne Tornberg ◽  
Sari E. Lauri ◽  
Matti S. Airaksinen ◽  
...  
Keyword(s):  
Reversal Potential ◽  
Membrane Conductance ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Glutamatergic Transmission ◽  
Action Potential Firing ◽  
Postsynaptic Currents ◽  
Hippocampal Ca1 ◽  
Synaptic Dynamics

GABAA receptor (GABA-AR)-mediated inhibition is critical for proper operation of neuronal networks. Synaptic inhibition either shifts the membrane potential farther away from the action potential firing threshold (hyperpolarizing inhibition) or via increase in the membrane conductance shunts the excitatory currents. However, the relative importance of these different forms of inhibition on the hippocampal function is unclear. To study the functional consequences of the absence of hyperpolarizing inhibition, we have used KCC2-deficient mice (KCC2hy/null) maintaining only 15–20% of the neuron-specific K-Cl-cotransporter. Gramicidin-perforated patch-clamp recordings in hippocampal CA1 pyramidal cells revealed that the reversal potential of the GABA-AR-mediated postsynaptic currents ( EGABA-A) was ∼20 mV more positive in KCC2hy/null mice than in wild-type (WT) animals. The basic glutamatergic transmission appeared unaltered in the KCC2hy/null mice, yet they displayed lowered threshold for stimulation-induced synchronous afterdischarges in the CA1 area. Also fatigue of field excitatory postsynaptic potentials/excitatory postsynaptic currents in response to repetitious stimulation was smaller in KCC2hy/null mice, indicating altered synaptic dynamics. Interestingly, this effect was present also under blockade of GABA-ARs and was dependent on the extracellular K+ concentration. Moreover, there were no differences in the levels of either long-term potentiation or long-term depression between the genotypes. The local hippocampal CA1 network can in several aspects maintain its functional viability even in the absence of hyperpolarizing inhibition in pyramidal cells. Our results underscore the central role of shunting type of inhibition in controlling the neuronal excitation/inhibition balance. Moreover, our data demonstrate a novel, unexpected role for the KCC2, namely the modulation of properties of glutamatergic transmission during repetitious afferent activity.

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