Functional properties and short‐term dynamics of unidirectional and reciprocal synaptic connections between layer 2/3 pyramidal cells and fast‐spiking interneurons in juvenile rat prefrontal cortex

The interactions between inhibitory fast‐spiking (FS) interneurons and excitatory pyramidal neurons contribute to the fundamental properties of cortical networks. An important role for FS interneurons in mediating rapid inhibition in local sensory and motor cortex microcircuits and processing thalamic inputs to the cortex has been shown in multiple reports; however, studies in the prefrontal cortex, a key neocortical region supporting working memory, are less numerous. In the present work, connections between layer 2/3 pyramidal cells and FS interneurons were studied with paired whole‐cell recordings in acute neocortical slices of the medial prefrontal cortex from juvenile rats. The connection rate between FS interneurons and pyramidal neurons was about 40% in each direction with 16% of pairs connected reciprocally. Excitatory and inhibitory connections had a high efficacy and a low neurotransmission failure rate. Sustained presynaptic activity decreased the amplitude of responses and increased the failure rate more in excitatory connections than in inhibitory connections. In the reciprocal connections between the FS and pyramidal neurons, inhibitory and excitatory neurotransmission was more efficient and had a lower failure rate than in the unidirectional connections; the differences increased during the train stimulation. These results suggest the presence of distinct preferential subnetworks between FS interneurons and pyramidal cells in the rat prefrontal cortex that might be specific for this cortical area.     

Input and frequency-specific entrainment of postsynaptic firing by IPSPs of perisomatic or dendritic origin

Correlated activity of cortical neurons underlies cognitive processes. Networks of several distinct classes of gamma-aminobutyric acid (GABA)ergic interneurons are capable of synchronizing cortical neurons at behaviourally relevant frequencies. Here we show that perisomatic and dendritic GABAergic inputs provided by two classes of GABAergic cells, fast spiking and bitufted interneurons, respectively, entrain the timing of postsynaptic spikes differentially in both pyramidal cells and interneurons at beta and gamma frequencies. Entrainment of pyramidal as well as regular spiking non-pyramidal cells was input site and inhibitory postsynaptic potential frequency dependent. Gamma frequency input from fast spiking cells entrained pyramidal cells on the positive phase of an intrinsic cellular theta oscillation, whereas input from bitufted cells was most effective in gamma frequency entrainment on the negative phase of the theta oscillation. The discharge of regular spiking interneurons was phased at gamma frequency by dendritic input from bitufted cells, but not by perisomatic input from fast spiking cells. Action potentials in fast spiking GABAergic neurons were phased at gamma frequency by both other fast spiking and bitufted cells, regardless of whether the presynaptic GABAergic input was at gamma or beta frequency. The interaction of cell type-specific intrinsic properties and location-selective GABAergic inputs could result in a spatio-temporally regulated synchronization and gating of cortical spike propagation in the network.     

Neurons of the lateral entorhinal cortex of the rhesus monkey: a Golgi, histochemical, and immunocytochemical characterization.

This study identifies the neuronal types of the rhesus monkey lateral entorhinal cortex (LEC) and discusses the importance of these data in the context of the connectional patterns of the LEC and the possible role of these cells in neurodegenerative diseases. These neuronal types were characterized with the aid of Golgi impregnation techniques. These characterizations were based upon their spine densities, dendritic arrays, and, where possible, axonal arborizations. The cells could be segregated into only spinous and sparsely spinous types. The most numerous spinous types were pyramidal neurons. Other spinous types included multipolar, vertical bipolar and bitufted, and vertical tripolar neurons. The sparsely spinous neuronal types consisted of multipolar, horizontal bipolar and bitufted, and neurogliaform cells. These cells were further classified with the aid of histochemical stains and immunocytochemical markers. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry stained multipolar, bipolar, and bitufted neurons. Stain for cytochrome oxidase (CO) was found in pyramidal and nonpyramidal cell types. Immunocytochemical techniques revealed several nonpyramidal neurons that contain somatostatin (Som) or substance P (SP). This study complements previous analyses of the neuronal components described in the LEC and adds further information about the distribution of selected neurochemicals within this cortex.     

Entorhinal cortical innervation of parvalbumin-containing neurons (basket and chandelier cells) in the rat ammon's horn

Physiological data suggest that in the CA1–CA3 hippocampal areas of rats, entorhinal cortical efferents directly influence the activity of interneurons, in addition to pyramidal cells. To verify this hypothesis, the following experiments were performed: 1) light microscopic double-immunostaining for parvalbumin and the anterograde tracer Phaseolus vulgaris-leucoagglutinin injected into the entorhinal cortex; 2) light and electron microscopic analysis of cleaved spectrin-immunostained (i.e., degenerating axons and boutons) hippocampal sections following entorhinal cortex lesion; and 3) an electron microscopic study of parvalbumin-immunostained hippocampal sections after entorhinal cortex lesion. The results demonstrate that in the stratum lacunosum-moleculare of the CA1 and CA3 regions, entorhinal cortical axons form asymmetric synaptic contacts on parvalbumin-containing dendritic shafts. In the stratum lacunosum-moleculare, parvalbumin-immunoreactive dendrites represent processes of GABAergic, inhibitory basket and chandelier cells; these interneurons innervate the perisomatic area and axon initial segments of pyramidal cells, respectively. A feed-forward activation of these neurons by the entorhinal input may explain the strong, short-latency inhibition of pyramidal cells. © 1996 Wiley-Liss, Inc.     

Electrophysiological and morphological characterization of cells in superficial layers of rat presubiculum

The presubiculum (PrS) plays critical roles in spatial information processing and memory consolidation and has also been implicated in temporal lobe epileptogenesis. Despite its involvement in these processes, a basic structure–function analysis of PrS cells remains far from complete. To this end, we performed whole‐cell recording and biocytin labeling of PrS neurons in layer (L)II and LIII to examine their electrophysiological and morphological properties. We characterized the cell types based on electrophysiological criteria, correlated their gross morphology, and classified them into distinct categories using unsupervised hierarchical cluster analysis. We identified seven distinct cell types: regular‐spiking (RS), irregular‐spiking (IR), initially bursting (IB), stuttering (Stu), single‐spiking (SS), fast‐adapting (FA), and late‐spiking (LS) cells, of which RS and IB cells were common to LII and LIII, LS cells were specific to LIII, and the remaining types were identified exclusively in LII. Recorded neurons were either pyramidal or nonpyramidal and, except for Stu cells, displayed spine‐rich dendrites. The RS, IB, and IR cells appeared to be projection neurons based on extension of their axons into LIII of the medial entorhinal area (MEA) and/or angular bundle. We conclude that LII and LIII of PrS are distinct in their neuronal populations and together constitute a more diverse population of neurons than previously suggested. PrS neurons serve as major drivers of circuits in superficial (LII–III) entorhinal cortex (ERC) and couple neighboring structures through robust afferentation, thereby substantiating the PrS's critical role in the parahippocampal region. J. Comp. Neurol. 521: 3116–3132, 2013. © 2013 Wiley Periodicals, Inc.     

Nicotinic activity layer specifically modulates synaptic potentiation in the mouse insular cortex

Nicotinic acetylcholine receptors (nAChRs) in the insular cortex play an important role in nicotine addiction, but its cellular and synaptic mechanisms underlying nicotine addiction still remain unresolved. In layer 5 pyramidal neurons of the mouse insular cortex, activation of nAChRs suppresses synaptic potentiation through enhancing GABAergic synaptic transmission via activation of β2‐containing nAChRs in non‐fast‐spiking (non‐FS) interneurons. However, it has not been addressed whether and how activation of nAChRs modulates synaptic plasticity in layers 3 and 6 pyramidal neurons of the insular cortex. In this study, I demonstrate that activation of nAChRs oppositely modulates synaptic potentiation in layers 3 and 6 pyramidal neurons of the insular cortex. In layer 3 pyramidal neurons, activation of nAChRs depressed synaptic potentiation induced by combination of presynaptic stimulation with postsynaptic depolarization (paired training) through enhancing GABAergic synaptic transmission via activation of β2‐containing nAChRs in non‐FS interneurons. By contrast, in layer 6 pyramidal neurons, activation of nAChRs enhanced synaptic potentiation through activating postsynaptic β2‐containing nAChRs. These results indicate, in different layers of the mouse insular cortex, paired training‐induced synaptic potentiation is oppositely regulated by activation of nAChRs which are located on GABAergic interneurons (layer 3) and on pyramidal neurons (layer 6). Thus, layer‐specific modulation of synaptic potentiation may be involved in cellular and synaptic mechanisms of insular cortical changes in nicotine addiction.     

Selective Functional Interactions between Excitatory and Inhibitory Cortical Neurons and Differential Contribution to Persistent Activity of the Slow Oscillation

The neocortex depends upon a relative balance of recurrent excitation and inhibition for its operation. During spontaneous Up states, cortical pyramidal cells receive proportional barrages of excitatory and inhibitory synaptic potentials. Many of these synaptic potentials arise from the activity of nearby neurons, although the identity of these cells is relatively unknown, especially for those underlying the generation of inhibitory synaptic events. To address these fundamental questions, we developed an in vitro submerged slice preparation of the mouse entorhinal cortex that generates robust and regular spontaneous recurrent network activity in the form of the slow oscillation. By performing whole-cell recordings from multiple cell types identified with green fluorescent protein expression and electrophysiological and/or morphological properties, we show that distinct functional subpopulations of neurons exist in the entorhinal cortex, with large variations in contribution to the generation of balanced excitation and inhibition during the slow oscillation. The most active neurons during the slow oscillation are excitatory pyramidal and inhibitory fast spiking interneurons, receiving robust barrages of both excitatory and inhibitory synaptic potentials. Weak action potential activity was observed in stellate excitatory neurons and somatostatin-containing interneurons. In contrast, interneurons containing neuropeptide Y, vasoactive intestinal peptide, or the 5-hydroxytryptamine (serotonin) 3a receptor, were silent. Our data demonstrate remarkable functional specificity in the interactions between different excitatory and inhibitory cortical neuronal subtypes, and suggest that it is the large recurrent interaction between pyramidal neurons and fast spiking interneurons that is responsible for the generation of persistent activity that characterizes the depolarized states of the cortex.     

Cellular neuroanatomy of rat presubiculum

The presubiculum, at the transition from the hippocampus to the cortex, is a key area for spatial information coding but the anatomical and physiological basis of presubicular function remains unclear. Here we correlated the structural and physiological properties of single neurons of the presubiculum in vitro. Unsupervised cluster analysis based on dendritic length and form, soma location, firing pattern and action potential properties allowed us to classify principal neurons into three major cell types. Cluster 1 consisted of a population of small regular spiking principal cells in layers II/III. Cluster 2 contained intrinsically burst firing pyramidal cells of layer IV, with a resting potential close to threshold. Cluster 3 included regular spiking cells of layers V and VI, and could be divided into subgroups 3.1 and 3.2. Cells of cluster 3.1 included pyramidal, multiform and inverted pyramidal cells. Cells of cluster 3.2 contained high‐resistance pyramidal neurons that fired readily in response to somatic current injection. These data show that presubicular principal cells generally conform to neurons of the periarchicortex. However, the presence of intrinsic bursting cells in layer IV distinguishes the presubicular cortex from the neighbouring entorhinal cortex. The firing frequency adaptation was very low for principal cells of clusters 1 and 3, a property that should assist the generation of maintained head direction signals in vivo.     

Normal anatomy and neurophysiology of the hippocampal formation.

This article reviews the anatomy and neurophysiology of the normal hippocampal formation, with emphasis on the human hippocampus. The hippocampus receives inputs from numerous limbic, cortical, and subcortical areas, primarily via the entorhinal cortex and subiculum. The primary pathway of neural activity entering the hippocampus is from entorhinal cortex via the perforant path to the dentate granule cells, with collaterals to CA1 and CA3 pyramidal cells. Mossy fibers from granule cells excite CA3 pyramidal cells and hilar interneurons. CA3 pyramidal cells excite CA1 pyramidal cells, with local and commissural excitatory collaterals exciting other CA3 pyramidal cells and septum. CA1 pyramidal cells send efferent fibers to subiculum, entorhinal cortex, and several subcortical areas. The principal excitatory synapses are glutamatergic, with two important postsynaptic receptor types, alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid and N-methyl-D-aspartate. The primary inhibitory transmitter is gamma-aminobutyric acid (GABA), with two postsynaptic receptor types, GABAA and GABAB. A number of modulatory transmitters and neuropeptides are also present. Inhibitory local synaptic networks in the hippocampus are described. Membrane ion channels in hippocampal neurons, particularly Ca2+ channels and K+ channels, are responsible for the regulation and patterning of neural activity. Long-term potentiation and axon sprouting are two experimental paradigms of neural plasticity presumably involved in hippocampal memory function.     

A novel population of calretinin-positive neurons comprises reelin-positive Cajal-Retzius cells in the hippocampal formation of the adult domestic pig

Calretinin-containing neurons in the hippocampal formation, including the subiculum, presubiculum, parasubiculum, and entorhinal cortex, were visualized with immunocytochemistry. Calretinin immunoreactivity was present exclusively in non-principal cells. The largest immunoreactive cell population was found in the outer half of the molecular layer of the dentate gyrus and in the stratum lacunosum-moleculare of Ammon's horn. A proportion of these cells were also immunoreactive for reelin, a Cajal-Retzius cell marker. Similar calretinin-positive cells were found in the molecular layer of the subicular complex and entorhinal cortex. In the parasubiculum, a few immunoreactive bipolar and multipolar cells could be observed in the superficial and deep pyramidal cell layers. In the entorhinal cortex, bipolar and multipolar calretinin-positive cells were frequent in layer II, and large numbers of multipolar cells in layer V were immunoreactive. Electron microscopic analysis showed that somata of calretinin-positive cells contained either round nuclei with smooth nuclear envelopes or nuclei with multiple deep infoldings. Immunoreactive dendrites were smooth varicose, and the apposing axon terminals formed both symmetric and asymmetric synapses. Zonula adherentia were observed between calretinin-positive dendrites. Calretinin-positive axon terminals formed two types of synapses. Axon terminals with asymmetric synapses were found close to the hippocampal fissure, whereas axon terminals forming symmetric synapses innervated spiny dendrites in both the molecular layer of the dentate gyrus and in stratum lacunosum-moleculare of Ammon's horn. Calretinin-positive axon terminals formed both symmetric and asymmetric synapses with calretinin-positive dendrites. In conclusion, calretinin-positive neurons form two major subpopulations in the adult domestic pig hippocampus: (1) a gamma-aminobutyric acid (GABA)ergic subpopulation of local circuit neurons that innervates distal dendrites of principal cells in both the dentate gyrus and in Ammon's horn; and (2) Cajal-Retzius type cells close to the hippocampal fissure, as well as in the molecular layer of the subicular complex and entorhinal cortex.     

The indusium griseum and anterior hippocampal continuation in the rat

The morphology and connections of the indusium griseum (IG) and anterior hippocampal continuation (AHC) suggest that this cortex contains analogues to several portions of the hippocampal formation. Whereas the outer neuronal layer of this cortex is made up of cells which are similar in structure to the neurons of the granule cell layer of the dentate gyrus, the three successively deeper layers contain morphological analogues to the neurons of the dentate hilus, Ammon's horn, and the subiculum, respectively. The neurons within each of these four layers of the AHC and IG have afferent and efferent connections which are quite similar to the connections of their hippocampal counterparts. Thus, the granule cells of the IG and AHC receive laminar inputs from the entorhinal cortex, the IG-AHC itself, and the supramammillary region. Each of these three classes of inputs ends at successively more proximal positions on the dendritic tree of these granule cells. Other inputs to this region include those from the septal nuclei and the olfactory bulb. The deeper layers of the IG and AHC receive several inputs, including those from the thalamic and septal nuclei and the entorhinal cortex. The efferent cell bodies of the IG and AHC are segregated in such a way that the granule cells appear to give rise to only short connections, while the hilar cells project to the granule cells, the intermediate pyramidal neurons project to other portions of the IG and AHC and to the olfactory bulb, and the deep pyramidal neurons project to the diencephalon. These results demonstrate that the IG-AHC is a continuation of the hippocampal formation.     

Neurophysiology of the caudally directed hippocampal efferent system in the rat: Projections to the subicular complex

We performed experiments studying the responses of rat subicular and entorhinal neurons to electrical stimulation of the fornix and hippocampus. Four main results were obtained: (1) extracellular recordings from principal neurons showed prolonged inhibition in response to stimulation, and intracellular recordings showed prominent IPSPs; (2) neither fornical nor commissural afferents were necessary for the inhibitory responses; they were present even in animals that had received prior surgical sections of the fornix and hippocampal commissures; (3) antidromic responses to fornix or hippocampal stimulation were recorded in neurons of the subicular complex; and (4) 3 cells in the subicular and entorhinal cortex were encountered that showed some of the properties associated with interneurons. The results suggest that principal neurons of the subicular complex share a number of properties with hippocampal pyramidal cells, including intrinsic recurrent inhibitory circuitry. Further study is required to determine the pathway for entorhinal inhibitory responses.     

Autoradiographic localization of estradiol-binding neurons in the rat hippocampal formation and entorhinal cortex

This study has examined the distribution of [3H]estradiol and [1 alpha,2 alpha-3H]testosterone uptake in the hippocampal formation and entorhinal cortex of male and female rats. In both males and females, [3H]estradiol-binding neurons in Ammon's horn are located deep in stratum pyramidale and may correspond either to polymorphic interneurons or to early maturing pyramidal cells. Interneurons of strata oriens, lucidum and radiatum of Ammon's horn and of stratum moleculare of the subiculum also bind [3H]estradiol, as do basket cell interneurons in the polymorphic, infragranular layer of the dentate gyrus. While no granule cells appear to accumulate [3H]estradiol, these cells may be affected transsynaptically by gonadal steroids via their afferent contacts with the entorhinal cortex, which, of the areas examined, contains the greatest number of [3H]estradiol-binding neurons. While relatively few neurons concentrate [3H]estradiol in the hippocampal formation, these are localized to specific subpopulations, which may enhance their functional significance. Because there is no significant nuclear accumulation of [3H]-alpha-testosterone in either the entorhinal cortex or hippocampal formation, it appears that aromatase enzyme activity is not a major contributor to estrogen receptor occupancy in adult rats.     

Reduced nicotinamide adenine dinucleotide phosphate-diaphorase/nitric oxide synthase profiles in the human hippocampal formation and perirhinal cortex

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-stained profiles were evaluated throughout the human hippocampal formation (i. e., dentate gyrus, Ammon's horn, subicular complex, entorhinal cortex) and perirhinal cortex. NADPH-d staining revealed pleomorphic cells, fibers, and blood vessels. Within the entorhinal and the perirhinal cortices, darkly stained (type 1) NADPH-d pyramidal, fusiform, bipolar, and multipolar neurons with extensive dendrites were scattered mainly within deep layers and subjacent white matter. Moderately stained (type 2) NADPH-d round or oval neurons were seen mainly in layers II and III of the entorhinal and perirhinal cortices, in the dentate gyrus polymorphic layer, in the CA fields stratum pyramidal and radiatum, and in the subicular complex. The distribution of type 2 cells was more abundant in the perirhinal cortex compared to the hippocampal formation. Lightly stained (type 3) NADPH-d pyramidal and oval neurons were distributed in CA4, the entorhinal cortex medial subfields, and the amygdalohippocampal transition area. Sections concurrently stained for NADPH-d and nitric oxide synthase (NOS) revealed that all type 1 neurons coexpressed NOS, whereas types 2 and 3 were NOS immunonegative. NADPH-d fibers were heterogeneously distributed within the different regions examined and were frequently in close apposition to reactive blood vessels. The greatest concentration of fibers was in layers III and V–VI of the entorhinal and perirhinal cortices, dentate gyrus polymorphic and molecular layers, and CA1 and CA4. A band of fibers coursing within CA1 divided into dorsal and ventral bundles to reach the presubiculum and entorhinal cortex, respectively. Although the distribution of NADPH-d fibers was conserved across all ages examined (28–98 years), we observed an increase in the density of fiber staining in the aged cases. These results may be relevant to our understanding of selective vulnerability of neuronal systems within the human hippocampal formation in aging and in neurodegenerative diseases. © 1995 Wiley-Liss, Inc.     

Neuronal classes in the isocortex of a monotreme,the Australian echidna (Tachyglossus aculeatus)

We have used Valverde-Golgi and Golgi-Colonnier techniques to analyze cortical neuronal morphology in four regions (frontal cortex, primary motor cortex, primary somatosensory cortex, primary visual cortex) of the isocortex of the echidna (Tachyglossus aculeatus). Eight classes of neurons could be identified--pyramidal, spinous bipolar, aspinous bipolar, spinous bitufted, aspinous bitufted, spinous multipolar, aspinous multipolar and neurogliaform. All except the pyramidal neurons were morphologically similar to neuronal classes seen in eutherian and metatherian isocortex. Pyramidal neurons made up a small proportion of all cortical neurons encountered in our preparations of echidna cortex (34% in visual cortex, 35% in somatosensory cortex, 41% in frontal cortex and 49% in motor cortex) compared to both reported values in eutherian cortex and values we found in rat cortex impregnations prepared in an identical fashion to the echidna material (75% in rat motor and 78% in rat somatosensory cortex). Many pyramidal neurons in the echidna isocortex were atypical (30-42% depending on region) with inverted somata, short or branching apical dendrites and/or few basal dendrites, very different from the usual pyramidal neuron morphology in eutherian cortex. Dendritic spine density on apical and basal dendrites of echidna pyramidal neurons in somatosensory cortex and apical dendrites of motor cortex pyramidal neurons was also lower than that found in the rat. The present findings are consistent with both pyramidal neurons and the many diverse types of non-pyramidal neurons having already emerged as discrete morphological entities very early in mammalian cortical evolution, at the time of divergence of the therian and prototherian lineage.     

Responses of rat subicular neurons to convergent stimulation of lateral entorhinal cortex and CA1 in vivo

There has been little electrophysiological examination of the afferent projection from lateral entorhinal cortex to dorsal subiculum. Here we provide evidence that synaptic inputs from lateral entorhinal cortex and CA1 converge onto single dorsal subicular neurons in vivo. Subicular responses to CA1 stimulation consisted of excitation and/or long-duration inhibition. Neurons excited by CA1 activation usually showed inhibition to entorhinal stimulation. The latter inhibition was usually of short duration, however, long duration inhibition was seen in a significant proportion of responses. Entorhinal stimulation produced excitatory responses in four bursting cells and it was these cells that also tended to show the longest inhibition. Only bursting cells could be driven antidromically by entorhinal stimulation. Biocytin-filled multipolar and pyramidal cells displayed excitation-inhibition sequences to CA1 and inhibition to entorhinal stimulation. These data strongly suggest that subicular inhibitory neurons receive excitatory input from CA1 and display mutual inhibition. The source of entorhinal-evoked inhibition is less clear. The relative sparseness of observed entorhinal-evoked responses suggests that the input to dorsal subiculum from any one part of lateral entorhinal cortex is spatially restricted. These data show that excitation-inhibition sequences can be seen in subicular pyramidal and multipolar cells and that single subicular neurons receive convergent inputs from CA1 and entorhinal cortex. We show for the first time that bursting cells can be driven both orthodromically and antidromically by direct entorhinal stimulation. These data support the existence of a reciprocal excitatory connection between lateral entorhinal cortex and dorsal subiculum and suggest further that this connection may involve only bursting subicular neurons.     

Transition in subicular burst firing neurons from epileptiform activity to suppressed state by feedforward inhibition

The subiculum, a para‐hippocampal structure positioned between the cornu ammonis 1 subfield and the entorhinal cortex, has been implicated in temporal lobe epilepsy in human patients and in animal models of epilepsy. The structure is characterized by the presence of a significant population of burst firing neurons that has been shown previously to lead epileptiform activity locally. Phase transitions in epileptiform activity in neurons following a prolonged challenge with an epileptogenic stimulus has been shown in other brain structures, but not in the subiculum. Considering the importance of the subicular burst firing neurons in the propagation of epileptiform activity to the entorhinal cortex, we have explored the phenomenon of phase transitions in the burst firing neurons of the subiculum in an in vitro rat brain slice model of epileptogenesis. Whole‐cell patch‐clamp and extracellular field recordings revealed a distinct phenomenon in the subiculum wherein an early hyperexcitable state was followed by a late suppressed state upon continuous perfusion with epileptogenic 4‐aminopyridine and magnesium‐free medium. The suppressed state was characterized by inhibitory post‐synaptic potentials in pyramidal excitatory neurons and bursting activity in local fast‐spiking interneurons at a frequency of 0.1–0.8 Hz. The inhibitory post‐synaptic potentials were mediated by GABA_A receptors that coincided with excitatory synaptic inputs to attenuate action potential discharge. These inhibitory post‐synaptic potentials ceased following a cut between the cornu ammonis 1 and subiculum. The suppression of epileptiform activity in the subiculum thus represents a homeostatic response towards the induced hyperexcitability. Our results suggest the importance of feedforward inhibition in exerting this homeostatic control.     

Responses of rat subicular neurons to convergent stimulation of lateral entorhinal cortex and CA1 in vivo

There has been little electrophysiological examination of the afferent projection from lateral entorhinal cortex to dorsal subiculum. Here we provide evidence that synaptic inputs from lateral entorhinal cortex and CA1 converge onto single dorsal subicular neurons in vivo. Subicular responses to CA1 stimulation consisted of excitation and/or long-duration inhibition. Neurons excited by CA1 activation usually showed inhibition to entorhinal stimulation. The latter inhibition was usually of short duration, however, long duration inhibition was seen in a significant proportion of responses. Entorhinal stimulation produced excitatory responses in four bursting cells and it was these cells that also tended to show the longest inhibition. Only bursting cells could be driven antidromically by entorhinal stimulation. Biocytin-filled multipolar and pyramidal cells displayed excitation–inhibition sequences to CA1 and inhibition to entorhinal stimulation. These data strongly suggest that subicular inhibitory neurons receive excitatory input from CA1 and display mutual inhibition. The source of entorhinal-evoked inhibition is less clear. The relative sparseness of observed entorhinal-evoked responses suggests that the input to dorsal subiculum from any one part of lateral entorhinal cortex is spatially restricted. These data show that excitation–inhibition sequences can be seen in subicular pyramidal and multipolar cells and that single subicular neurons receive convergent inputs from CA1 and entorhinal cortex. We show for the first time that bursting cells can be driven both orthodromically and antidromically by direct entorhinal stimulation. These data support the existence of a reciprocal excitatory connection between lateral entorhinal cortex and dorsal subiculum and suggest further that this connection may involve only bursting subicular neurons.     

GABAergic contributions to gating,timing, and phase precession of hippocampal neuronal activity during theta oscillations

Successful spatial exploration requires gating, storage, and retrieval of spatial memories in the correct order. The hippocampus is known to play an important role in the temporal organization of spatial information. Temporally ordered spatial memories are encoded and retrieved by the firing rate and phase of hippocampal pyramidal cells and inhibitory interneurons with respect to ongoing network theta oscillations paced by intra‐ and extrahippocampal areas. Much is known about the anatomical, physiological, and molecular characteristics as well as the connectivity and synaptic properties of various cell types in the hippocampal microcircuits, but how these detailed properties of individual neurons give rise to temporal organization of spatial memories remains unclear. We present a model of the hippocampal CA1 microcircuit based on observed biophysical properties of pyramidal cells and six types of inhibitory interneurons: axo‐axonic, basket, bistratistified, neurogliaform, ivy, and oriens lacunosum‐moleculare cells. The model simulates a virtual rat running on a linear track. Excitatory transient inputs come from the entorhinal cortex (EC) and the CA3 Schaffer collaterals and impinge on both the pyramidal cells and inhibitory interneurons, whereas inhibitory inputs from the medial septum impinge only on the inhibitory interneurons. Dopamine operates as a gate‐keeper modulating the spatial memory flow to the PC distal dendrites in a frequency‐dependent manner. A mechanism for spike‐timing‐dependent plasticity in distal and proximal PC dendrites consisting of three calcium detectors, which responds to the instantaneous calcium level and its time course in the dendrite, is used to model the plasticity effects. The model simulates the timing of firing of different hippocampal cell types relative to theta oscillations, and proposes functional roles for the different classes of the hippocampal and septal inhibitory interneurons in the correct ordering of spatial memories as well as in the generation and maintenance of theta phase precession of pyramidal cells (place cells) in CA1. The model leads to a number of experimentally testable predictions that may lead to a better understanding of the biophysical computations in the hippocampus and medial septum. © 2012 Wiley Periodicals, Inc.