Functional connectivity from ca3 to the ipsilateral and contralateral ca1 in the rat dorsal hippocampus

doi:10.1016/0306-4522(93)90566-X

Neuroscience

Volume 56, Issue 1, September 1993, Pages 101-108

https://doi.org/10.1016/0306-4522(93)90566-X Get rights and content

Abstract

Anatomical advances have led to a reappraisal of the organization of hippocampal circuitry. However, it is not clear whether the functional connectivity is fully determined by the anatomical connectivity or whether it is significantly modified by feed-forward inhibition and modulatory inputs. Therefore, we have mapped CA1 responses evoked by stimulation of ipsilateral and contralateral CA3in vivo. Population spike amplitude and threshold were plotted to produce response maps. All CA3 subregions projected diffusely to ipsilateral CA1. However, a pattern of maximal response emerged. Caudal CA3 stimulation evoked the maximal responses septally, while rostral CA3 responses were maximal temporally. The ipsilateral CA3 response maps were compared with those produced by stimulation at the homotopic point in the contralateral CA3. The CA1 areas of maximal functional connectivity were the same implying that there is convergence of the input to CA1 from homotopic CA3 sites in the two hippocampi.

Although a response in CA1 was evoked widely, our results suggest that the functional connectivity is ordered, within and between the dorsal hippocampi, and that it is consistent with the recent anatomical data. The present findings allow more precise study of the propagation of normal and abnormal neuronal activity, within and between the dorsal hippocampi. Information on the site and speed of propagation of neuronal activity would be necessary for the development of a physiologically realistic model of hippocampal computation.

Reference (28)

AmaralD.G. et al.
The three-dimensional organization of the hippocampal formation: a review of anatomical data
Neuroscience
(1989)
AndersenP. et al.
Functional characteristics of unmyelinated fibres in the hippocampal cortex
Brain Res.
(1978)
BartesaghiR. et al.
Interlamellar transfer of impulses in the hippocampal formation
Expl Neurol.
(1983)
Buzsa´kiG.
Feed-forward inhibition in the hippocampal formation
Prog. Neurobiol.
(1984)
Buzsa´kiG. et al.
Convergence of associational and commissural pathways on CA1 pyramidal cells of the rat hippocampus
Brain Res.
(1982)
KnowlesW.D. et al.
The initiation and spread of epileptiform bursts in thein vitro hippocampal slice
Neuroscience
(1987)
LaurbergS. et al.
Associational and commissural collaterals of neurons in the hippocampal formation (hilus fasciae dentatae and subfield CA3)
Brain Res.
(1981)
SkredeK.K. et al.
The transverse hippocampal slice: a well defined cortical structure maintainedin vitro
Brain Res.
(1971)
AndersenP.
Interhippocampal impulses. IV. A correlation of some functional and structural properties of the interhippocampal fibres in cat, rabbit and rat
Acta physiol. scand.
(1960)
AndersenP. et al.
Lamellar organization of hippocampal excitatory pathways
Expl Brain Res.
(1971)

AndersenP. et al.

Thresholds of action potentials evoked by synapses on the dendrites of pyramidal cells in the rat hippocampusin vitro

J. Physiol., Lond.

(1987)

AshwoodT.J. et al.

Intracellular electrophysiology of CA1 pyramidal neurones in slices of the kainic acid lesioned hippocampus of the rat

Expl Brain Res.

(1986)

BlissT.V.P. et al.

Long-term potentiation in commissural and Schaffer projections to hippocampal CA1 cells: anin vivo study in the rat

J. Physiol., Lond.

(1983)

BraceH.M. et al.

Long-term changes in hippocampal physiology and in learning ability of rats after intrahippocampal tetanus toxin

J. Physiol., Lond.

(1985)

Cited by (37)

All-optical physiology resolves a synaptic basis for behavioral timescale plasticity
2023, Cell
Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals.
The unreasonable effectiveness of small neural ensembles in high-dimensional brain
2019, Physics of Life Reviews
Citation Excerpt :
Thus, an ensemble of single neurons in the CA1 can receive simultaneously the same synaptic input (Fig. 13b, left). These neurons have different topology and functional connectivity [26], therefore, their response to the same input can be different. Experimental in-vivo results show that long term potentiation can significantly increase the spike transfer rate in the CA3-CA1 pathway [24].
Complexity is an indisputable, well-known, and broadly accepted feature of the brain. Despite the apparently obvious and widely-spread consensus on the brain complexity, sprouts of the single neuron revolution emerged in neuroscience in the 1970s. They brought many unexpected discoveries, including grandmother or concept cells and sparse coding of information in the brain.
In machine learning for a long time, the famous curse of dimensionality seemed to be an unsolvable problem. Nevertheless, the idea of the blessing of dimensionality becomes gradually more and more popular. Ensembles of non-interacting or weakly interacting simple units prove to be an effective tool for solving essentially multidimensional and apparently incomprehensible problems. This approach is especially useful for one-shot (non-iterative) correction of errors in large legacy artificial intelligence systems and when the complete re-training is impossible or too expensive.
These simplicity revolutions in the era of complexity have deep fundamental reasons grounded in geometry of multidimensional data spaces. To explore and understand these reasons we revisit the background ideas of statistical physics. In the course of the 20th century they were developed into the concentration of measure theory. The Gibbs equivalence of ensembles with further generalizations shows that the data in high-dimensional spaces are concentrated near shells of smaller dimension. New stochastic separation theorems reveal the fine structure of the data clouds.
We review and analyse biological, physical, and mathematical problems at the core of the fundamental question: how can high-dimensional brain organise reliable and fast learning in high-dimensional world of data by simple tools? To meet this challenge, we outline and setup a framework based on statistical physics of data.
Two critical applications are reviewed to exemplify the approach: one-shot correction of errors in intellectual systems and emergence of static and associative memories in ensembles of single neurons. Error correctors should be simple; not damage the existing skills of the system; allow fast non-iterative learning and correction of new mistakes without destroying the previous fixes. All these demands can be satisfied by new tools based on the concentration of measure phenomena and stochastic separation theory.
We show how a simple enough functional neuronal model is capable of explaining: i) the extreme selectivity of single neurons to the information content of high-dimensional data, ii) simultaneous separation of several uncorrelated informational items from a large set of stimuli, and iii) dynamic learning of new items by associating them with already “known” ones. These results constitute a basis for organisation of complex memories in ensembles of single neurons.
Degeneration of cholinergic basal forebrain nuclei after focally evoked status epilepticus
2019, Neurobiology of Disease
Citation Excerpt :
In fact, NBM and MSN receives direct afferents from the piriform cortex (Mesulam and Mufson, 1984; Mesulam, 2013), the MSN and DBB receive afferents mainly from the hippocampus (Haghdoost-Yazdi et al., 2009). The apparent discrepancy that, the already in the group with low severity SE there was a strong contralateral cell loss in MSN, and even more in DBB, compared with NBM, might be due to the higher connection of DBB and MSN with the hippocampus via commissural pathway (e.g. Finnerty and Jefferys, 1993). In fact, in this study the contralateral hippocampus was damaged as well, and this is in line with the occurrence of contralateral AHS in patients with TLE who experience severe and frequent seizures (Meencke et al., 1996).
Status epilepticus (SE) of limbic onset might cause degenerative phenomena in different brain structures, and may be associated with chronic cognitive and EEG effects. In the present study SE was evoked focally by microinfusing picomolar doses of cyclothiazide+bicuculline into the anterior extent of the piriform cortex (APC) in rats, the so-called area tempestas, an approach which allows to evaluate selectively the effects of seizure spreading through the natural anatomical circuitries up to secondary generalization. In the brain of rats submitted to SE we analyzed neuronal density, occurrence of degenerative phenomena (by Fluoro-Jade B-FJB- staining) and expression of heat shock protein-70 (HSP-70) in the piriform cortex, the hippocampus and ventromedial thalamus. We further analyzed in detail, the loss of cholinergic neurons, and the presence of FJB- and HSP-70 positive neurons in basal forebrain cholinergic areas, i.e. the medial septal nucleus (MSN, Ch1), the diagonal band of Broca (DBB, Ch2 and Ch3) and the Nucleus basalis of Meynert (NBM, Ch4). In fact, these nuclei are strictly connected with limbic structures, and play a key pivotal role in different cognitive functions and vigilance. Although recent studies begun to investigate these nuclei in experimental epilepsy and in persons with epilepsy, conflicting results were obtained so far. We showed that after severe and long-lasting, focally induced limbic SE there is a significant cell loss within all of the abovementioned cholinergic nuclei ipsi- and contra-laterally to the infusion site. In parallel, these nuclei show also FJB and heat shock protein-70 expression. Those effects vary depending on the single nucleus assessed and on the severity of the SE seizure score. We also showed the occurrence of cell loss and degenerative phenomena in limbic cortex, hippocampus and limbic thalamic areas. These novel findings show direct evidence of SE-induced neuronal damage which is solely due to seizure activity ruling out potential confounding effects produced by systemic pro-convulsant neurotoxins. A damage to basal forebrain cholinergic nuclei, which may underlie cognitive alterations, is documented for the first time in a model of SE triggered focally.
Structured Synaptic Connectivity between Hippocampal Regions
2014, Neuron
Citation Excerpt :
(1) For broad presynaptic labeling, as previously described (Kim et al., 2012), Cre-independent pre-mGRASP (aavCAG-pre-mGRASP-mCerulean, available in Addgene) and Cre-dependent “switch on” post-mGRASP AAV (aavCAG-Jx-rev-post-mGRASP-2A-dTomato, available in Addgene) (∼2 × 1012 pfu/ml) were injected to left CA3 and right CA1 (P60∼75), respectively, after in utero electroporation of paavCAG-iCre (2 μg/μl) into hippocampal CA1 progenitor cells in the right lateral ventricle (E15.5). To obtain clearly separate expression of pre- and postsynaptic mGRASP components we used the commissural projections from CA3 to CA1 that have been shown to roughly follow the same topographic organization and functional connectivity of ipsilateral projections (Finnerty and Jefferys, 1993). ( 2) To label specific temporally matched subpopulations, CA3 and CA1 progenitor cells of both ventricles were both transduced with rAAV expressing Cre recombinase (aavCAG-iCre, ∼2 × 1012 pfu/ml) in utero (E15.5).
The organization of synaptic connectivity within a neuronal circuit is a prime determinant of circuit function. We performed a comprehensive fine-scale circuit mapping of hippocampal regions (CA3-CA1) using the newly developed synapse labeling method, mGRASP. This mapping revealed spatially nonuniform and clustered synaptic connectivity patterns. Furthermore, synaptic clustering was enhanced between groups of neurons that shared a similar developmental/migration time window, suggesting a mechanism for establishing the spatial structure of synaptic connectivity. Such connectivity patterns are thought to effectively engage active dendritic processing and storage mechanisms, thereby potentially enhancing neuronal feature selectivity.
Mechanism of highly synchronized bilateral hippocampal activity
2014, Experimental Neurology
Citation Excerpt :
The human dorsal hippocampal commissure (DHC) is a sizable tract which travels between bilateral hippocampal formations (Colnat-Coulbois et al., 2010; Gloor et al., 1993; Rosenzweig et al., 2011). Depth electrode EEG recordings show that secondarily generalized MTLE occurs in the bilateral hippocampus before surrounding structures, suggesting the DHC is responsible for contralateral spread of seizures (Finnerty et al., 1993; Gloor et al., 1993; Rosenzweig et al., 2011). While the DHC is clearly present in humans (Colnat-Coulbois et al. 2010), it is somewhat small in rodents.
In vivo studies of epileptiform discharges in the hippocampi of rodents have shown that bilateral seizure activity can sometimes be synchronized with very small delays (< 2 ms). This observed small time delay of epileptiform activity between the left and right CA3 regions is unexpected given the physiological propagation time across the hemispheres (> 6 ms). The goal of this study is to determine the mechanisms of this tight synchronization with in-vitro electrophysiology techniques and computer simulations. The hypothesis of a common source was first eliminated by using an in-vitro preparation containing both hippocampi with a functional ventral hippocampal commissure (VHC) and no other tissue. Next, the hypothesis that a noisy baseline could mask the underlying synchronous activity between the two hemispheres was ruled out by low noise in-vivo recordings and computer simulation of the noisy environment. Then we built a novel bilateral CA3 model to test the hypothesis that the phenomenon of very small left-to-right propagation delay of seizure activity is a product of epileptic cell network dynamics. We found that the commissural tract connectivity could decrease the delay between seizure events recorded from two sides while the activity propagated longitudinally along the CA3 layer thereby yielding delays much smaller than the propagation time between the two sides. The modeling results indicate that both recurrent and feedforward inhibition were required for shortening the bilateral propagation delay and depended critically on the length of the commissural fiber tract as well as the number of cells involved in seizure generation. These combined modeling/experimental studies indicate that it is possible to explain near perfect synchronization between the two hemispheres by taking into account the structure of the hippocampal network.
Loss of activity-dependent Arc gene expression in the retrosplenial cortex after hippocampal inactivation: Interaction in a higher-order memory circuit
2012, Neurobiology of Learning and Memory
Citation Excerpt :
The bilateral impact of acute unilateral hippocampal inactivation on Arc transcription in the RSC may be explained by the expression pattern observed in CA1, where Arc was eliminated in the inactivated hemisphere, but partially spared in the contralateral one. The partial decrease of Arc expression in the VEH infused CA1 may be due to loss of commissural CA3 or CA1 inputs from the TTX infused hemisphere (Finnerty & Jefferys, 1993; van Groen & Wyss, 1990). This partial CA1 activity could propagate in RSC bilaterally via its reciprocal connections with the contralateral RSC and subicular complex (Wyss & van Groen, 1992).
The rodent hippocampus is well known for its role in spatial navigation and memory, and recent evidence points to the retrosplenial cortex (RSC) as another element of a higher order spatial and mnemonic circuit. However, the functional interplay between hippocampus and RSC during spatial navigation remains poorly understood. To investigate this interaction, we examined cell activity in the RSC during spatial navigation in the water maze before and after acute hippocampal inactivation using expression of two immediate-early genes (IEGs), Arc and Homer 1a (H1a). Adult male rats were trained in a spatial water maze task for 4 days. On day 5, the rats received two testing/training sessions separated by 20 min. Eight minutes before the second session, different groups of rats received bilateral intrahippocampal infusion of tetrodotoxin (TTX), muscimol (MUS), or vehicle. Another group of rats (uni-TTX) received infusion of TTX in one hippocampus and vehicle in the other. Signals from Arc and H1a RNA probes correspond to the post- and pre-infusion sessions, respectively. Bilateral TTX and MUS impaired spatial memory, as expected, and decreased Arc expression in CA1 of hippocampus. Importantly, bilateral inactivation of hippocampus resulted in loss of behavior-induced Arc expression in RSC. Despite a lateralized effect in CA1, Arc expression was equivalently and bilaterally decreased in RSC of uni-TTX rats, consistent with a network level interaction between hippocampus and RSC. We conclude that the loss of hippocampal input alters activity of RSC neurons and compromises their ability to engage plastic processes dependent on IEG expression.

View all citing articles on Scopus

View full text

Functional connectivity from ca3 to the ipsilateral and contralateral ca1 in the rat dorsal hippocampus

Abstract

Neuroscience

Brain Res.

Expl Neurol.

Prog. Neurobiol.

Brain Res.

Neuroscience

Brain Res.

Brain Res.

Interhippocampal impulses. IV. A correlation of some functional and structural properties of the interhippocampal fibres in cat, rabbit and rat

Acta physiol. scand.

Lamellar organization of hippocampal excitatory pathways

Expl Brain Res.

Thresholds of action potentials evoked by synapses on the dendrites of pyramidal cells in the rat hippocampusin vitro

J. Physiol., Lond.

Intracellular electrophysiology of CA1 pyramidal neurones in slices of the kainic acid lesioned hippocampus of the rat

Expl Brain Res.

Long-term potentiation in commissural and Schaffer projections to hippocampal CA1 cells: anin vivo study in the rat

J. Physiol., Lond.

Long-term changes in hippocampal physiology and in learning ability of rats after intrahippocampal tetanus toxin

J. Physiol., Lond.