Parvalbumin-containing Basket Cells Research Articles

Different output properties of perisomatic region-targeting interneurons in the basal amygdala.

The perisomatic region of principal neurons in cortical regions is innervated by three types of GABAergic interneuron, including parvalbumin-containing basket cells (PVBCs) and axo-axonic cells (AACs), as well as cholecystokinin and type 1 cannabinoid receptor-expressing basket cells (CCK/CB1BCs). These perisomatic inhibitory cell types can also be found in the basal nucleus of the amygdala, however, their output properties are largely unknown. Here, we performed whole-cell recordings in morphologically identified interneurons in slices prepared from transgenic mice, in which the GABAergic cells could be selectively targeted. Investigating the passive and active membrane properties of interneurons located within the basal amygdala revealed that the three interneuron types have distinct single-cell properties. For instance, the input resistance, spike rate, accommodation in discharge rate, or after-hyperpolarization width at the half maximal amplitude separated the three interneuron types. Furthermore, we performed paired recordings from interneurons and principal neurons to uncover the basic features of unitary inhibitory postsynaptic currents (uIPSCs). Although we found no difference in the magnitude of responses measured in the principal neurons, the uIPSCs originating from the distinct interneuron types differed in rise time, failure rate, latency, and short-term dynamics. Moreover, the asynchronous transmitter release induced by a train of action potentials was typical for the output synapses of CCK/CB1BCs. Our results suggest that, despite the similar uIPSC magnitudes originating from the three perisomatic inhibitory cell types, their distinct release properties together with the marked differences in their spiking characteristics may contribute to accomplish specific functions in amygdala network operation.

Perisomatic GABAergic synapses of basket cells effectively control principal neuron activity in amygdala networks.

Efficient control of principal neuron firing by basket cells is critical for information processing in cortical microcircuits, however, the relative contribution of their perisomatic and dendritic synapses to spike inhibition is still unknown. Using in vitro electrophysiological paired recordings we reveal that in the mouse basal amygdala cholecystokinin- and parvalbumin-containing basket cells provide equally potent control of principal neuron spiking. We performed pharmacological manipulations, light and electron microscopic investigations to show that, although basket cells innervate the entire somato-denditic membrane surface of principal neurons, the spike controlling effect is achieved primarily via the minority of synapses targeting the perisomatic region. As the innervation patterns of individual basket cells on their different postsynaptic partners show high variability, the impact of inhibitory control accomplished by single basket cells is also variable. Our results show that both basket cell types can powerfully regulate the activity in amygdala networks predominantly via their perisomatic synapses.

Identified Cellular Correlates of Neocortical Ripple and High-Gamma Oscillations during Spindles of Natural Sleep

SummaryUltra-high-frequency network events in the hippocampus are instrumental in a dialogue with the neocortex during memory formation, but the existence of transient ∼200 Hz network events in the neocortex is not clear. Our recordings from neocortical layer II/III of freely behaving rats revealed field potential events at ripple and high-gamma frequencies repeatedly occurring at troughs of spindle oscillations during sleep. Juxtacellular recordings identified subpopulations of fast-spiking, parvalbumin-containing basket cells with epochs of firing at ripple (∼200 Hz) and high-gamma (∼120 Hz) frequencies detected during spindles and centered with millisecond precision at the trough of spindle waves in phase with field potential events but phase shifted relative to pyramidal cell firing. The results suggest that basket cell subpopulations are involved in spindle-nested, high-frequency network events that hypothetically provide repeatedly occurring neocortical temporal reference states potentially involved in mnemonic processes.

Embryonic interneurons from the medial, but not the caudal ganglionic eminence trigger ocular dominance plasticity in adult mice.

The maturation of cortical inhibition provided by parvalbumin-containing basket cells derived from the medial ganglionic eminence (MGE) is a key event in starting the enhanced visual cortical plasticity during the critical period. Although it is generally assumed that a further increase in inhibition closes the critical period again, it was recently shown that embryonic interneurons derived from the MGE can induce an additional, artificial critical period when injected into the visual cortex of young mice. It has, however, remained open whether this effect was indeed specific for MGE-derived cells, and whether critical period-like plasticity could also be induced in fully adult animals. To clarify these issues, we injected explants from either the MGE or the caudal ganglionic eminence (CGE) into the visual cortices of fully adult mice, and performed monocular deprivation 33days later for 4days. Animals implanted with MGE cells, but not with CGE cells, showed marked ocular dominance plasticity. Immunohistochemistry confirmed that the injected cells from both sources migrated far in the host cortex, that most developed into neurons producing GABA, and that only cells from the MGE expressed parvalbumin. Thus, our results confirm that the plasticity-inducing effect of embryonic interneurons is specific for cells from the MGE, and is independent of the host animal's age.

Target-selectivity of parvalbumin-positive interneurons in layer II of medial entorhinal cortex in normal and epileptic animals.

The medial entorhinal cortex layer II (MEClayerII ) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII . However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII . However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII . Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. © 2015 Wiley Periodicals, Inc.

Input-Output Features of Anatomically Identified CA3 Neurons during Hippocampal Sharp Wave/Ripple Oscillation In Vitro

Hippocampal sharp waves and the associated ripple oscillations (SWRs) are implicated in memory processes. These network events emerge intrinsically in the CA3 network. To understand cellular interactions that generate SWRs, we detected first spiking activity followed by recording of synaptic currents in distinct types of anatomically identified CA3 neurons during SWRs that occurred spontaneously in mouse hippocampal slices. We observed that the vast majority of interneurons fired during SWRs, whereas only a small portion of pyramidal cells was found to spike. There were substantial differences in the firing behavior among interneuron groups; parvalbumin-expressing basket cells were one of the most active GABAergic cells during SWRs, whereas ivy cells were silent. Analysis of the synaptic currents during SWRs uncovered that the dominant synaptic input to the pyramidal cell was inhibitory, whereas spiking interneurons received larger synaptic excitation than inhibition. The discharge of all interneurons was primarily determined by the magnitude and the timing of synaptic excitation. Strikingly, we observed that the temporal structure of synaptic excitation and inhibition during SWRs significantly differed between parvalbumin-containing basket cells, axoaxonic cells, and type 1 cannabinoid receptor (CB1)-expressing basket cells, which might explain their distinct recruitment to these synchronous events. Our data support the hypothesis that the active current sources restricted to the stratum pyramidale during SWRs originate from the synaptic output of parvalbumin-expressing basket cells. Thus, in addition to gamma oscillation, these GABAergic cells play a central role in SWR generation.

Reply: Impaired mitochondrial function abolishes gamma oscillations in the hippocampus through an effect on fast-spiking interneurons

ARTICLE Sir, We appreciate the letter of Whittaker et al . (2011) who report on the effects of metabolic stress on the properties of excitatory pyramidal cells and fast-spiking inhibitory interneurons during gamma oscillations. The authors combined extra- and intracellular electrophysiological recordings and pharmacology in rat hippocampal slices in vitro . Gamma oscillations are generally thought to represent a temporal matrix of higher brain functions and have been observed in all cortical brain structures, including the hippocampus (Bartos et al. , 2007; Uhlhaas and Singer, 2010; Whittington et al. , 2011). In hippocampal neuronal networks, the precise interaction of several types of inhibitory GABAergic interneurons (releasing neurotransmitter, γ-aminobutyric acid) and excitatory pyramidal cells is essential for the establishment of gamma oscillations. Inhibitory GABAergic interneurons are characterized by much higher action potential firing rates than excitatory pyramidal cells (Hajos et al. , 2009). Highly active inhibitory interneurons are the axo-axonic cells and the parvalbumin-containing basket cells that have been reported to generate action potentials at ∼40 Hz during gamma oscillations or at ∼200 Hz during sharp-wave ripple activity (Ylinen et al. , 1995; Penttonen et al. , 1998; Klausberger et al. , 2003). In many in vitro studies, gamma oscillations have been induced in hippocampal slice preparations by bath application of cholinergic receptor agonists (acetylcholine or carbachol; cholinergic model) or glutamatergic receptor agonist, kainic …

Nanodomain Coupling between Ca2+ Channels and Ca2+ Sensors Promotes Fast and Efficient Transmitter Release at a Cortical GABAergic Synapse

It is generally thought that transmitter release at mammalian central synapses is triggered by Ca2+ microdomains, implying loose coupling between presynaptic Ca2+ channels and Ca2+ sensors of exocytosis. Here we show that Ca2+ channel subunit immunoreactivity is highly concentrated in the active zone of GABAergic presynaptic terminals of putative parvalbumin-containing basket cells in the hippocampus. Paired recording combined with presynaptic patch pipette perfusion revealed that GABA release at basket cell-granule cell synapses is sensitive to millimolar concentrations of the fast Ca2+ chelator BAPTA but insensitive to the slow Ca2+ chelator EGTA. These results show that Ca2+ source and Ca2+ sensor are tightly coupled at this synapse, with distances in the range of 10-20 nm. Models of Ca2+ inflow-exocytosis coupling further reveal that the tightness of coupling increases efficacy, speed, and temporal precision of transmitter release. Thus, tight coupling contributes to fast feedforward and feedback inhibition in the hippocampal network.

Cell type dependence and variability in the short-term plasticity of EPSCs in identified mouse hippocampal interneurones.

Synapses exhibit different short-term plasticity patterns and this behaviour influences information processing in neuronal networks. We tested how the short-term plasticity of excitatory postsynaptic currents (EPSCs) depends on the postsynaptic cell type, identified by axonal arborizations and molecular markers in the hippocampal CA1 area. Three distinct types of short-term synaptic behaviour (facilitating, depressing and combined facilitating-depressing) were defined by fitting a dynamic neurotransmission model to the data. Approximately 75 % of the oriens-lacunosum-moleculare (O-LM) interneurones received facilitating EPSCs, but in three of 12 O-LM cells EPSCs also showed significant depression. Over 90 % of the O-LM cells were immunopositive for somatostatin and mGluR1alpha and all tested cells were decorated by strongly mGluR7a positive axon terminals. Responses in eight of 12 basket cells were described well with a model involving only depression, but the other cells displayed combined facilitating-depressing EPSCs. No apparent difference was found between the plasticity of EPSCs in cholecystokinin- or parvalbumin-containing basket cells. In oriens-bistratified cells (O-Bi), two of nine cells showed facilitating EPSCs, another two depressing, and the remaining five cells combined facilitating-depressing EPSCs. Seven of 10 cells tested for somatostatin were immunopositive, but mGluR1alpha was detectable only in two of 11 tested cells. Furthermore, most O-Bi cells projected to the CA3 area and the subiculum, as well as outside the hippocampal formation. Postsynaptic responses to action potentials recorded in vivo from a CA1 place cell were modelled, and revealed great differences between and within cell types. Our results demonstrate that the short-term plasticity of EPSCs is cell type dependent, but with significant heterogeneity within all three interneurone populations.

Mu opioid receptors are in discrete hippocampal interneuron subpopulations.

In the rat hippocampal formation, application of mu opioid receptor (MOR) agonists disinhibits principal cells, promoting excitation-dependent processes such as epileptogenesis and long-term potentiation. However, the precise location of MORs in particular inhibitory circuits, has not been determined, and the roles of MORs in endogenous functioning are unclear. To address these issues, the distribution of MOR-like immunoreactivity (-li) was examined in several populations of inhibitory hippocampal neurons in the CA1 region using light and electron microscopy. We found that MOR-li was present in many parvalbumin-containing basket cells, but absent from cholecystokinin-labeled basket cells. MOR-li was also commonly in interneurons containing somatostatin-li or neuropeptide Y-li that resembled the "oriens-lacunosum-moleculare" (O-LM) interneurons innervating pyramidal cell distal dendrites. Finally, MOR-li was in some vasoactive intestinal peptide- or calretinin-containing profiles resembling interneurons that primarily innervate other interneurons. These findings indicate that MOR-containing neurons form a neurochemically and functionally heterogeneous subset of hippocampal GABAergic neurons. MORs are most frequently on interneurons that are specialized to inhibit pyramidal cells, and are on a limited number of interneurons that target other interneurons. Moreover, the distribution of MORs to different neuronal types in several laminae, some relatively far from endogenous opioids, suggests normal functional roles that are different from the actions seen with exogenous agonists such as morphine.

Subcellular localization of the K + channel subunit Kv3.1b in selected rat CNS neurons

Voltage-gated potassium channels constitute the largest group of heteromeric ion channels discovered to date. Over 20 genes have been isolated, encoding different channel subunit proteins which form functional tetrameric K + channels. We have analyzed the subcellular localization of subunit Kv3.1b, a member of the Kv3 ( Shaw-like) subfamily, in rat brain at the light and electron microscopic level, using immunocytochemical detection. Detailed localization was carried out in specific neurons of the neocortex, hippocampus and cerebellum. The identity of Kv3.1b-positive neurons was established using double labeling with markers for specific neuronal populations. In the neocortex, the Kv3.1b subunit was expressed in most parvalbumin-containing bipolar, basket or chandelier cells, and in some bipolar or double bouquet neurons containing calbindin. In the hippocampus, Kv3.1b was expressed in many parvalbumin-containing basket cells, as well as in calbindin-positive neurons in the stratum oriens, and in a small number of interneurons that did not stain for either parvalbumin or calbindin. Kv3.1b protein was not present in pyramidal cells in the neocortex and the hippocampus, but these cells were outlined by labeled presynaptic terminals from interneuron axons that surround the postsynaptic cell. In the cerebellar cortex, granule cells were the only population expressing the channel protein. Careful examination of individual granule cells revealed a non-uniform distribution of Kv3.1 staining on the somata: circular bands of labeling were present in the vicinity of the axon hillock. In cortical and hippocampal interneurons, as well as in cerebellar granule cells, the Kv3.1b subunit was present in somatic and unmyelinated axonal membranes and adjacent cytoplasm, as well as in the most proximal portion of dendritic processes, but not throughout most of the dendrite. Labeling was also seen in the terminals of labeled axons, but not at a higher concentration than in other parts of the axon. The distribution in the cells analyzed supports a role in action potential transmission by regulating action potential duration.

Morphological evidence that hypothalamic substance P-containing afferents are capable of filtering the signal flow in the monkey hippocampal formation

This study in the African green monkey (Cercopithecus aethiops) was designed to characterize the neurochemical features of hippocampal nonpyramidal neurons that are specific synaptic targets of substance P-containing projective neurons located in the supramammillary nucleus. Our previous studies provided evidence for an excitatory nature to this hypothalamo-hippocampal pathway and described the mode of termination of these afferents on hippocampal principal neurons. The present correlated light and electron microscopic immunocytochemical analysis, using the nickel-diaminobenzidine/diaminobenzidine double-labeling technique, revealed that this hippocampal afferent system establishes multiple, exclusively asymmetric synapses with three specific subpopulations of nonpyramidal cells: (1) a small portion of parvalbumin-containing basket cells located periodically in or adjacent to the granule cell layer of the dentate gyrus, which therefore inhibit only a subpopulation of granule cells; (2) some of the calbindin-immunoreactive local circuit neurons located in the hilar area; and (3) calbindin-positive cells occurring exclusively in the stratum molecular of the middle portion of the CA3 subfield. Postembedding studies revealed that the aforementioned calbindin-containing cells are GABAergic inhibitory neurons. Our studies indicate that hypothalamic afferents can effectively filter the information flow at different levels of the excitatory signal loop in the monkey hippocampal formation. Dentate granule cells, which are only stimulated by hypothalamic afferents, will transfer excitatory signals differently than those that are controlled by a feedforward inhibitory mechanism initiated by these fibers. In the CA3 subfield, the signal flow can again be depressed by those pyramidal neurons that are inhibited by calbindin-containing cells receiving an excitatory hypothalamic input.