Showing papers on "Interneuron published in 2006"
TL;DR: Recent data that are beginning to illuminate the origins and specification of distinct subgroups of cortical interneurons are discussed.
Abstract: GABA-containing interneurons are crucial to both the development and function of the cerebral cortex. Unlike cortical projection neurons, which have a relatively conserved set of characteristics, interneurons include multiple phenotypes that vary on morphological, physiological and neurochemical axes. This diversity, and the relatively late, context-dependent maturation of defining features, has challenged efforts to uncover the transcriptional control of cortical interneuron development. Here, we discuss recent data that are beginning to illuminate the origins and specification of distinct subgroups of cortical interneurons.
887 citations
TL;DR: New advances in understanding the mammalian CPGs are discussed with a focus on experiments that address the overall network structure as well as the identification of CPG neurons.
Abstract: Intrinsic spinal networks, known as central pattern generators (CPGs), control the timing and pattern of the muscle activity underlying locomotion in mammals. This review discusses new advances in understanding the mammalian CPGs with a focus on experiments that address the overall network structure as well as the identification of CPG neurons. I address the identification of excitatory CPG neurons and their role in rhythm generation, the organization of flexor-extensor networks, and the diverse role of commissural interneurons in coordinating left-right movements. Molecular and genetic approaches that have the potential to elucidate the function of populations of CPG interneurons are also discussed.
842 citations
TL;DR: After dopaminergic depletion, cortical inputs and GABA interneurons might imbalance striatal projection neurons and represent two novel nondopaminergic mechanisms that might secondarily contribute to the pathophysiology of Parkinson's disease.
Abstract: The striatum receives massive cortical excitatory inputs and is densely innervated by dopamine. Striatal projection neurons form either the direct or indirect pathways. Models of Parkinson's disease propose that dopaminergic degeneration imbalances both pathways, although direct electrophysiological evidence is lacking. Here, striatal neurons were identified by electrophysiological criteria and Neurobiotin labeling combined with either immunohistochemistry or in situ hybridization. Their spontaneous discharge activity and spike response to cortical stimulation were recorded in vivo in anesthetized rats rendered hemi-parkinsonian by 6-hydroxydopamine. We showed that striatonigral neurons (direct pathway) were inhibited whereas striatopallidal neurons (indirect pathway) were activated by dopaminergic lesion. We also identified, with antidromic stimulations, corticostriatal neurons that preferentially innervate striatonigral or striatopallidal neurons and showed that dopaminergic depletion selectively decreased the spontaneous activity of the former. Therefore, dopamine degeneration induces a cascade of imbalances that spread out of the basal ganglia and affect the whole basal ganglia-thalamo-cortical circuits. Fast-spiking GABA interneurons provide potent feedforward inhibition of striatal projection neurons. We showed here that these interneurons narrowed the time window of the responses of projection neurons to cortical stimulation. In the dopamine-depleted striatum, because the intrinsic activity of these interneurons was not altered, their feedforward inhibition worsened the striatal imbalance. Indeed, the time window of the evoked responses was narrower for striatonigral neurons and wider for striatopallidal neurons. Therefore, after dopaminergic depletion, cortical inputs and GABA interneurons might imbalance striatal projection neurons and represent two novel nondopaminergic mechanisms that might secondarily contribute to the pathophysiology of Parkinson's disease.
397 citations
TL;DR: An important role for inhibition is outlined in regulating the frequency of the locomotor CPG rhythm, and it is suggested that V1 neurons may have an evolutionarily conserved role in controlling the speed of vertebrate locomotor movements.
Abstract: The neuronal networks that generate vertebrate movements such as walking and swimming are embedded in the spinal cord. These networks, which are referred to as central pattern generators (CPGs), are ideal systems for determining how ensembles of neurons generate simple behavioural outputs. In spite of efforts to address the organization of the locomotor CPG in walking animals, little is known about the identity and function of the spinal interneuron cell types that contribute to these locomotor networks. Here we use four complementary genetic approaches to directly address the function of mouse V1 neurons, a class of local circuit inhibitory interneurons that selectively express the transcription factor Engrailed1. Our results show that V1 neurons shape motor outputs during locomotion and are required for generating 'fast' motor bursting. These findings outline an important role for inhibition in regulating the frequency of the locomotor CPG rhythm, and also suggest that V1 neurons may have an evolutionarily conserved role in controlling the speed of vertebrate locomotor movements.
372 citations
TL;DR: It is shown that GABA(A) receptor-mediated inhibition in mature interneurons of the hippocampal dentate gyrus is shunting rather than hyperpolarizing, which may confer increased robustness to gamma oscillations in the brain.
330 citations
TL;DR: Conditional inactivation of Sp8 in the embryonic ventral telencephalon reveals a requirement for the normal generation of these interneuron subtypes, and Sp8 conditional mutants exhibit an increase in cell death within the lateral ganglionic eminence and rostral migratory stream, indicating that Sp8 contributes to olfactory bulbinterneuron diversity by regulating the survival, migration, and molecular specification of neuroblasts/interneurons.
241 citations
TL;DR: Although no statistical difference in the horizontal ladder walking was found between the groups, the increase in collateral sprouting and in the number of contacts correlated with the functional recovery, suggesting cell body treatment can promote plasticity of the injured CNS and may be a valuable treatment approach in conjunction with local regeneration promoting strategies.
Abstract: Although regeneration of injured axons is inhibited within the adult CNS, moderate recovery can be found in patients and animals with incomplete spinal cord injury (SCI). This can be partly attributed to sprouting of spared and injured axons, rostral and caudal to the lesion, respectively. Recently, it has been reported that following a thoracic SCI such sprouting can result in indirect reconnections of the lesioned axons to caudal targets via propriospinal interneurons (PrI). Here, we attempted to further promote this spontaneous repair mechanism by applying the neurotrophic factor BDNF (brain-derived neurotrophic factor), in the vicinity of the cell bodies of lesioned corticospinal neurons or NT-3, intrathecally to the cervical spinal cord. We performed a dorsal over-hemisection at the thoracic spinal cord sparing only the left ventrolateral quadrant. This type of lesion did not promote sprouting of injured corticospinal axons or re-routing via commissural PrI. Also, in rats that received NT-3 at the cervical enlargement, no increase in sprouting was found. However, animals receiving BDNF at the cell bodies of lesioned corticospinal neurons showed a significant increase in collateral sprouting and in the number of contacts with PrI. This was not observed when BDNF was administered to unlesioned animals. Although no statistical difference in the horizontal ladder walking was found between the groups, the increase in collateral sprouting and in the number of contacts correlated with the functional recovery. Hence, cell body treatment can promote plasticity of the injured CNS and may be a valuable treatment approach in conjunction with local regeneration promoting strategies.
215 citations
TL;DR: Direct morphological evidence is provided that parvalbumin-containing GABAergic neurons in layer 2/3 of the cat visual cortex form dense and far-ranging networks through dendritic gap junctions that supports the precise synchronization of neuronal populations with differing feature preferences thereby providing a temporal frame for the generation of distributed representations.
Abstract: Gap junctions are common between cortical GABAergic interneurons but little is known about their quantitative distribution along dendritic profiles. Here, we provide direct morphological evidence that parvalbumin-containing GABAergic neurons in layer 2/3 of the cat visual cortex form dense and far-ranging networks through dendritic gap junctions. Gap junction-coupled networks of parvalbumin neurons were visualized using connexin36 immunohistochemistry and confocal laser-scanning microscopy (CLSM). The direct correspondence of connexin36-immunopositve puncta and gap junctions was confirmed by examining the same structures in both CLSM and electron microscopy. Single parvalbumin neurons with large somata (> or =200 microm2) formed 60.3 +/- 12.2 (mean +/- SD) gap junctions with other cells whereby these contacts were not restricted to proximal dendrites but occurred at distances of up to 380 microm from the soma. In a Sholl analysis of large-type parvalbumin neurons, 21.9 +/- 7.9 gap junctions were within 50 microm of the soma, 21.7 +/- 7.6 gap junctions in a segment between 50 and 100 microm, 11.2 +/- 4.7 junctions between 100 and 150 microm, and 5.6 +/- 3.6 junctions were in more distal segments. Serially interconnected neurons could be traced laterally in a boundless manner through multiple gap junctions. Comparison to the orientation-preference columns revealed that parvalbumin-immunoreactive cells distribute randomly whereby their large dendritic fields overlap considerably and cover different orientation columns. It is proposed that this dense and homogeneous electrical coupling of interneurons supports the precise synchronization of neuronal populations with differing feature preferences thereby providing a temporal frame for the generation of distributed representations.
187 citations
TL;DR: It is demonstrated that MGE cells grafted into one location of the neonatal rodent brain migrate widely into cortex, and it is inferred that graft-derived cells integrate into local circuits and function as GABA-producing inhibitory cells.
Abstract: Embryonic medial ganglionic eminence (MGE) cells transplanted into the adult brain can disperse, migrate, and differentiate to neurons expressing GABA, the primary inhibitory neurotransmitter. It has been hypothesized that grafted MGE precursors could have important therapeutic applications increasing local inhibition, but there is no evidence that MGE cells can modify neural circuits when grafted into the postnatal brain. Here we demonstrate that MGE cells grafted into one location of the neonatal rodent brain migrate widely into cortex. Grafted MGE-derived cells differentiate into mature cortical interneurons; the majority of these new interneurons express GABA. Based on their morphology and expression of somatostatin, neuropeptide Y, parvalbumin, or calretinin, we infer that graft-derived cells integrate into local circuits and function as GABA-producing inhibitory cells. Whole-cell current-clamp recordings obtained from MGE-derived cells indicate firing properties typical of mature interneurons. Moreover, patch-clamp recordings of IPSCs on pyramidal neurons in the host brain, 30 and 60 d after transplantation, indicated a significant increase in GABA-mediated synaptic inhibition in regions containing transplanted MGE cells. In contrast, synaptic excitation is not altered in the host brain. Grafted MGE cells, therefore, can be used to modify neural circuits and selectively increase local inhibition. These findings could have important implications for reparative cell therapies for brain disorders.
185 citations
TL;DR: It is shown here that the chemokine stromal-derived factor 1 (SDF-1; CXCL12) is expressed in the main invasion route for cortical interneurons in the SVZ/IZ, and this results represent the first evidence for a molecular interaction between precursors of projection neurons and invading interneuronons during corticogenesis.
Abstract: Most cortical interneurons are generated in the subpallial ganglionic eminences and migrate tangentially to their final destinations in the neocortex. Within the cortex, interneurons follow mainly stereotype routes in the subventricular zone/intermediate zone (SVZ/IZ) and in the marginal zone. It has been suggested that interactions between invading interneurons and locally generated projection neurons are implicated in the temporal and spatial regulation of the invasion process. However, so far experimental evidence for such interactions is lacking. We show here that the chemokine stromal-derived factor 1 (SDF-1; CXCL12) is expressed in the main invasion route for cortical interneurons in the SVZ/IZ. Most SDF-1-positive cells are proliferating and express the homeodomain transcription factors Cux1 and Cux2. Using MASH-1 mutant mice in concert with the interneuron marker DLX, we exclude that interneurons themselves produce the chemokine in an autocrine manner. We conclude that the SDF-1-expressing cell population represents the precursors of projection neurons during their transition and amplification in the SVZ/IZ. Using mice lacking the SDF-1 receptor CXCR4 or Pax6, we demonstrate that SDF-1 expression in the cortical SVZ/IZ is essential for recognition of this pathway by interneurons. These results represent the first evidence for a molecular interaction between precursors of projection neurons and invading interneurons during corticogenesis.
184 citations
TL;DR: The results suggest that the properties of local intracortical inhibitory networks are modified by sensory experiences, and perisomatic inhibition mediated by PV-positive basket cells is pruned by sensory deprivation.
Abstract: During postnatal development, sensory experiences play critical roles in the refinement of cortical connections. However, both the process of postnatal experience-dependent maturation of neocortical inhibitory networks and its underlying mechanisms remain elusive. Here, we examined the differential properties of intracortical inhibitory networks of layer IV in “sensory-spared” and “sensory-deprived” cortices of glutamate acid decarboxylase 67 (GAD67)–green fluorescent protein (GFP) (Δneo) and wild-type mouse. Our results showed that row D whisker trimming (WT) begun at postnatal day 7 (P7), but not after P15, induced a robust reduction of parvalbumin (PV) expression, measured by the PV/GFP ratio and PV cell densities, in the deprived barrels. WT also induced a robust reduction in the number of inhibitory perisomatic varicosities and synaptic GAD65/67 immunoreactivities in spiny neurons of the deprived barrels. Although the GAD65/67 expressions in interneurons were also downregulated in the deprived barrels, the GFP expression remained unchanged. Patch-clamp recording from spiny cells showed a 1.5-fold reduction of intracortical evoked IPSCs (eIPSCs) in deprived versus spared cortices. The reduction in eIPSCs occurred via changes in presynaptic properties and unitary IPSC amplitudes. Miniature IPSCs showed subtle but significant differences between the two experimental conditions. In addition, properties of the IPSCs in deprived barrels resemble those of IPSCs recorded in immature brains (P7). Together, these results suggest that the properties of local intracortical inhibitory networks are modified by sensory experiences. Perisomatic inhibition mediated by PV-positive basket cells is pruned by sensory deprivation.
TL;DR: The studies indicate that PDE 10A is associated with post-synaptic membranes of the medium spiny neurons, suggesting that the specialized compartmentation of PDE10A enables the regulation of intracellular signaling from glutamatergic and dopaminergic inputs to these neurons.
TL;DR: It is shown that a single, multisegmental interneuron is responsible for the pre- and postsynaptic inhibition of auditory neurons in singing crickets (Gryllus bimaculatus), and this neuron represents a corollary dischargeinterneuron that provides a neuronal basis for the central control of sensory responses.
Abstract: How do animals discriminate self-generated from external stimuli during behavior and prevent desensitization of their sensory pathways? A fundamental concept in neuroscience states that neural signals, termed corollary discharges or efference copies, are forwarded from motor to sensory areas. Neurons mediating these signals have proved difficult to identify. We show that a single, multisegmental interneuron is responsible for the pre- and postsynaptic inhibition of auditory neurons in singing crickets (Gryllus bimaculatus). Therefore, this neuron represents a corollary discharge interneuron that provides a neuronal basis for the central control of sensory responses.
TL;DR: Stereological evidence of fewer GABAergic interneurons, fewer gephyrin-immunoreactive punctae, and reduced frequency of spontaneous IPSCs and miniature IPSCs confirmed that layer II stellate cell hyperexcitability is attributable, at least in part, to reduced inhibitory synaptic input.
Abstract: Temporal lobe epilepsy is the most common type of epilepsy in adults, and its pathophysiology remains unclear. Layer II stellate cells of the entorhinal cortex, which are hyperexcitable in animal models of temporal lobe epilepsy, provide the predominant synaptic input to the hippocampal dentate gyrus. Previous studies have ascribed the hyperexcitability of layer II stellate cells to GABAergic interneurons becoming "dormant" after disconnection from their excitatory synaptic inputs, which has been reported to occur during preferential loss of layer III pyramidal cells. We used whole-cell recording from slices of entorhinal cortex in pilocarpine-treated epileptic rats to test the dormant interneuron hypothesis. Hyperexcitability appeared as multiple action potentials and prolonged depolarizations evoked in layer II stellate cells of epileptic rats but not controls. However, blockade of glutamatergic synaptic transmission caused similar percentage reductions in the frequency of spontaneous IPSCs in layer II stellate cells of control and epileptic rats, suggesting similar levels of excitatory synaptic input to GABAergic interneurons. Direct recordings and biocytin labeling revealed two major types of interneurons in layer III whose excitatory synaptic drive in epileptic animals was undiminished. Interneurons in layer III did not appear to be dormant; therefore, we tested whether loss of GABAergic synapses might underlie hyperexcitability of layer II stellate cells. Stereological evidence of fewer GABAergic interneurons, fewer gephyrin-immunoreactive punctae, and reduced frequency of spontaneous IPSCs and miniature IPSCs (recorded in tetrodotoxin) confirmed that layer II stellate cell hyperexcitability is attributable, at least in part, to reduced inhibitory synaptic input.
TL;DR: It is proposed that a switch in Ascl1 function enables the cogeneration of inhibitory and excitatory sensory interneurons from a common pool of dorsal progenitors.
Abstract: Sensory information from the periphery is integrated and transduced by excitatory and inhibitory interneurons in the dorsal spinal cord. Recent studies have identified a number of postmitotic factors that control the generation of these sensory interneurons. We show that Gsh1/2 and Ascl1 (Mash1), which are expressed in sensory interneuron progenitors, control the choice between excitatory and inhibitory cell fates in the developing mouse spinal cord. During the early phase of neurogenesis, Gsh1/2 and Ascl1 coordinately regulate the expression of Tlx3, which is a critical postmitotic determinant for dorsal glutamatergic sensory interneurons. However, at later developmental times, Ascl1 controls the expression of Ptf1a in dIL(A) progenitors to promote inhibitory neuron differentiation while at the same time upregulating Notch signaling to ensure the proper generation of dIL(B) excitatory neurons. We propose that this switch in Ascl1 function enables the cogeneration of inhibitory and excitatory sensory interneurons from a common pool of dorsal progenitors.
TL;DR: The study clearly demonstrated that changes in GABA(A) receptor distribution not only occur in the early postnatal cortex and hippocampal formation but also during later periods in the adolescent and aging brain.
TL;DR: This study studies in mice the expression patterns in differentiating and mature neocortical interneurons of 8 transcription factors, including 6 homeobox and 1 basic helix-loop-helix, to define the combinatorial codes of transcription factors that participate in regulating the specification and function of cortical interneuron subtypes.
Abstract: Most gamma-aminobutyric acidergic interneurons in the neocortex and hippocampus are derived from subpallial progenitors in the medial ganglionic eminence and migrate tangentially to the pallium, where they differentiate into a diverse set of neuronal subtypes. Toward elucidating the mechanisms underlying the generation of interneuron diversity, we have studied in mice the expression patterns in differentiating and mature neocortical interneurons of 8 transcription factors, including 6 homeobox (Dlx1, Dlx2, Dlx5, Arx, Lhx6, Cux2), 1 basic helix-loop-helix, (NPAS1), and 1 bZIP (MafB). Their patterns of expression change during interneuron differentiation and show distinct distributions within interneuron subpopulations in adult neocortex. This study is a first step to define the combinatorial codes of transcription factors that participate in regulating the specification and function of cortical interneuron subtypes.
TL;DR: In multicompartment O-LM interneuron models that incorporated IM, somatodendritic placement of Kv7 channels best reproduced experimentally measured IM, and the models suggest that Kv3- and KV7-mediated channels both rapidly activate during single APs; however, K v3 channels control rapid repolarization of the AP, whereas K v7 channels primarily control the interspike interval.
Abstract: The M-current ( I M), comprised of Kv7 channels, is a voltage-activated K+ conductance that plays a key role in the control of cell excitability. In hippocampal principal cells, I M controls action potential (AP) accommodation and contributes to the medium-duration afterhyperpolarization, but the role of I M in control of interneuron excitability remains unclear. Here, we investigated I M in hippocampal stratum oriens (SO) interneurons, both from wild-type and transgenic mice in which green fluorescent protein (GFP) was expressed in somatostatin-containing interneurons. Somatodendritic expression of Kv7.2 or Kv7.3 subunits was colocalized in a subset of GFP+ SO interneurons, corresponding to oriens-lacunosum moleculare (O-LM) cells. Under voltage clamp (VC) conditions at −30 mV, the Kv7 channel antagonists linopirdine/XE-991 abolished the I M amplitude present during relaxation from −30 to −50 mV and reduced the holding current ( I hold). In addition, 0.5 mm tetraethylammonium reduced I M, suggesting that I M was composed of Kv7.2-containing channels. In contrast, the Kv7 channel opener retigabine increased I M amplitude and I hold. When strongly depolarized in VC, the linopirdine-sensitive outward current activated rapidly and comprised up to 20% of the total current. In current-clamp recordings from GFP+ SO cells, linopirdine induced depolarization and increased AP frequency, whereas retigabine induced hyperpolarization and arrested firing. In multicompartment O-LM interneuron models that incorporated I M, somatodendritic placement of Kv7 channels best reproduced experimentally measured I M. The models suggest that Kv3- and Kv7-mediated channels both rapidly activate during single APs; however, Kv3 channels control rapid repolarization of the AP, whereas Kv7 channels primarily control the interspike interval.
TL;DR: The migration toward and within the hippocampus, and the maturation of their morphological and neurochemical characteristics are detailed, and potential mechanisms underlying the development of GABAergic interneurons are reviewed.
Abstract: Interneurons are GABAergic neurons responsible for inhibitory activity in the adult hippocampus, thereby controlling the activity of principal excitatory cells through the activation of postsynaptic GABAA receptors. Subgroups of GABAergic neurons innervate specific parts of excitatory neurons. This specificity indicates that particular interneuron subgroups are able to recognize molecules segregated on the membrane of the pyramidal neuron. Once these specific connections are established, a quantitative regulation of their strength must be performed to achieve the proper balance of excitation and inhibition. We will review when and where interneurons are generated. We will then detail their migration toward and within the hippocampus, and the maturation of their morphological and neurochemical characteristics. We will finally review potential mechanisms underlying the development of GABAergic interneurons.
TL;DR: It is shown here that ectopic grafting of SVZ tissue gave rise to two morphologically distinguishable cell types displaying oligodendrocytic or astrocyt characteristics, showing that committed interneuron precursors undergo glial differentiation outside their normal environment.
TL;DR: Contrary to other cerebellar types, GABAergic interneurons are produced by a common pool of progenitors, which maintain their full developmental potentialities up to late ontogenetic stages and adopt mature identities in response to local instructive cues.
Abstract: Different cerebellar phenotypes are generated according to a precise spatiotemporal schedule, in which projection neurons precede local interneurons. Glutamatergic neurons develop from the rhombic lip, whereas GABAergic neurons originate from the ventricular neuroepithelium. Progenitors in these germinal layers are committed toward specific phenotypes already at early ontogenetic stages. GABAergic interneurons are thought to derive from a subset of ventricular zone cells, which migrate in the white matter and proliferate up to postnatal life. During this period, different interneuron categories are produced according to an inside-out sequence, from the deep nuclei to the molecular layer (we show here that nuclear interneurons are also born during late embryonic and early postnatal days, after glutamatergic and GABAergic projection neurons). To ask whether distinct interneuron phenotypes share common precursors or derive from multiple fate-restricted progenitors, we examined the behavior of embryonic and postnatal rat cerebellar cells heterotopically/heterochronically transplanted to syngenic hosts. In all conditions, donor cells achieved a high degree of integration in the cerebellar cortex and deep nuclei and acquired GABAergic interneuron phenotypes appropriate for the host age and engraftment site. Therefore, contrary to other cerebellar types, which derive from dedicated precursors, GABAergic interneurons are produced by a common pool of progenitors, which maintain their full developmental potentialities up to late ontogenetic stages and adopt mature identities in response to local instructive cues. In this way, the numbers and types of inhibitory interneurons can be set by spatiotemporally patterned signals to match the functional requirements of developing cerebellar circuits.
TL;DR: It is shown that interneurons in the dorsal and middle hippocampus with putative monosynaptic connections with place cells recorded on the same tetrode share other properties with their pyramidal cell afferents, including the spatial scale of the place field of pyramid cell, a characteristic of the septotemporal level of the hippocampus from which the cells are recorded, and the rate of phase precession.
Abstract: Although hippocampal interneurons typically do not show discrete regions of elevated firing in an environment, such as seen in pyramidal cell place fields, they do exhibit significant spatial modulation (McNaughton et al., 1983a). Strong monosynaptic coupling between pyramidal neurons and nearby interneurons in the CA1 stratum pyramidale has been strongly implicated on the basis of significant, short-latency peaks in cross-correlogram plots (Csicsvari et al., 1998). Furthermore, interneurons receiving a putative monosynaptic connection from a simultaneously recorded pyramidal cell appear to inherit the spatial modulation of the latter (Marshall et al., 2002). Buzsaki and colleagues hypothesize that interneurons may also adopt the firing phase dynamics of their afferent place cells, which show a phase shift relative to the hippocampal theta rhythm as a rat passes through the place field ("phase precession"). This study confirms and extends the previous reports by showing that interneurons in the dorsal and middle hippocampus with putative monosynaptic connections with place cells recorded on the same tetrode share other properties with their pyramidal cell afferents, including the spatial scale of the place field of pyramidal cell, a characteristic of the septotemporal level of the hippocampus from which the cells are recorded, and the rate of phase precession, which is slower in middle regions. Furthermore, variations in pyramidal cell place field scale within each septotemporal level attributable to task variations are similarly associated with variations in interneuron place field scale. The available data strongly suggest that spatial selectivity of CA1 stratum pyramidale interneurons is inherited from a small cluster of local pyramidal cells and is not a consequence of spatially selective synaptic input from CA3 or other sources.
TL;DR: A combination of behavioral, electrophysiological, anatomical, and genetic data indicate an essential role for the Dα7 nAChR in giant fiber-mediated escape in Drosophila.
Abstract: Acetylcholine is the major excitatory neurotransmitter in the central nervous system of insects. Mutant analysis of the Dα7 nicotinic acetylcholine receptor (nAChR) ofDrosophila shows that it is required for the giant fiber-mediated escape behavior. The Dα7 protein is enriched in the dendrites of the giant fiber, and electrophysiological analysis of the giant fiber circuit showed that sensory input to the giant fiber is disrupted, as is transmission at an identified cholinergic synapse between the peripherally synapsing interneuron and the dorsal lateral muscle motor neuron. Moreover, we found thatgfA1, a mutation identified in a screen for giant fiber defects more than twenty years ago, is an allele ofDα7. Therefore, a combination of behavioral, electrophysiological, anatomical, and genetic data indicate an essential role for the Dα7 nAChR in giant fiber-mediated escape inDrosophila.
TL;DR: Noise from background synaptic input may enhance network excitability by increasing gain in pyramidal neurons with large sAHPs and reducing gain in inhibitory FS interneurons, depending on specific biophysical properties including the sAHP conductance.
Abstract: Neuronal firing is known to depend on the variance of synaptic input as well as the mean input current Several studies suggest that input variance, or “noise,” has a divisive effect, reducing the slope or gain of the firing frequency–current ( f–I ) relationship We measured the effects of current noise on f–I relationships in pyramidal neurons and fast-spiking (FS) interneurons in slices of rat sensorimotor cortex In most pyramidal neurons, noise had a multiplicative effect on the steady-state f–I relationship, increasing gain In contrast, noise reduced gain in FS interneurons Gain enhancement in pyramidal neurons increased with stimulus duration and was correlated with the amplitude of the slow afterhyperpolarization (sAHP), a major mechanism of spike-frequency adaptation The 5-HT2 receptor agonist α-methyl-5-HT reduced the sAHP and eliminated gain increases, whereas augmenting the sAHP conductance by spike-triggered dynamic-current clamp enhanced the gain increase These results indicate that the effects of noise differ fundamentally between classes of neocortical neurons, depending on specific biophysical properties including the sAHP conductance Thus, noise from background synaptic input may enhance network excitability by increasing gain in pyramidal neurons with large sAHPs and reducing gain in inhibitory FS interneurons
TL;DR: The distribution of Reelin is systematically mapped in adult rat brain using sensitive immunolabeling techniques and suggests abundant axoplasmic transport and secretion in pathways such as the retino‐collicular tract, the entorhino‐hippocampal (‘perforant’) path, the lateral olfactory tract or the parallel fiber system of the cerebellum.
Abstract: Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal (‘perforant’) path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits.
TL;DR: It is reported that BLA interneurons can be differentiated into four electrophysiologically distinct subtypes based on their intrinsic membrane properties and their response to afferent synaptic input.
Abstract: The basolateral amygdala (BLA) is critical for the generation of emotional behavior and the formation of emotional memory. Understanding the neuronal mechanisms that contribute to emotional information processing in the BLA will ultimately require knowledge of the anatomy and physiology of its constituent neurons. Two major cell classes exist in the BLA, pyramidal projection neurons and nonpyramidal interneurons. Although the properties of projection neurons have been studied in detail, little is known about the properties of BLA interneurons. We have used whole-cell patch clamp recording techniques to examine the physiological properties of 48 visually identified putative interneurons from the rat anterior basolateral amygdalar nucleus. Here, we report that BLA interneurons can be differentiated into four electrophysiologically distinct subtypes based on their intrinsic membrane properties and their response to afferent synaptic input. Interneuron subtypes were named according to their characteristic firing pattern generated in response to transient depolarizing current injection and were grouped as follows: 1) burst-firing interneurons (n = 13), 2) regular-firing interneurons (n = 11), 3) fast-firing interneurons (n = 10), and 4) stutter-firing interneurons (n = 14). Post hoc histochemical visualization confirmed that all 48 recorded neurons had morphological properties consistent with their being local circuit interneurons. Moreover, by using triple immunofluorescence (for biocytin, calcium-binding proteins, and neuropeptides) in conjunction with patch clamp recording, we further demonstrated that over 60% of burst-firing and stutter-firing interneurons also expressed the calcium-binding protein parvalbumin (PV(+)). These data demonstrate that interneurons of the BLA show both physiological and neurochemical diversity. Moreover, we demonstrate that the burst- and stutter-firing patterns positively correlate with PV(+) immunoreactivity, suggesting that these neurons may represent functionally distinct subpopulations.
TL;DR: A role for astrocyte-derived NO in injury to striatal-pallidal interneurons from Mn intoxication is suggested, as indicated by immunohistochemical staining for tyrosine hydroxylase.
TL;DR: A recurrent mechanism of gamma oscillations, whereby spike timing is controlled primarily by inhibition in pyramidal cells and by excitation in interneurons is supported.
Abstract: Gamma-frequency oscillations are prominent during active network states in the hippocampus An intrahippocampal gamma generator has been identified in the CA3 region To better understand the synaptic mechanisms involved in gamma oscillogenesis, we recorded action potentials and synaptic currents in distinct types of anatomically identified CA3 neurons during carbachol-induced (20-25 microM) gamma oscillations in rat hippocampal slices We wanted to compare and contrast the relationship between excitatory and inhibitory postsynaptic currents in pyramidal cells and perisomatic-targeting interneurons, cell types implicated in gamma oscillogenesis, as well as in other interneuron subtypes, and to relate synaptic currents to the firing properties of the cells We found that phasic synaptic input differed between cell classes Most strikingly, the dominant phasic input to pyramidal neurons was inhibitory, whereas phase-coupled perisomatic-targeting interneurons often received a strong phasic excitatory input Differences in synaptic input could account for some of the differences in firing rate, action potential phase precision, and mean action potential phase angle, both between individual cells and between cell types There was a strong positive correlation between the ratio of phasic synaptic excitation to inhibition and firing rate over all neurons and between the phase precision of excitation and action potentials in interneurons Moreover, mean action potential phase angle correlated with the phase of the peak of the net-estimated synaptic reversal potential in all phase-coupled neurons The data support a recurrent mechanism of gamma oscillations, whereby spike timing is controlled primarily by inhibition in pyramidal cells and by excitation in interneurons
TL;DR: Some of the striatal projection neurons and the GABA-parvalbumin and cholinergic interneurons were removed by apoptosis in the aftermath of METH, suggesting an imbalance in the populations of striatal neurons may lead to functional abnormalities in the output and processing of neural information in this part of the brain.
TL;DR: Time-lapse imaging and in vivo labelling indicated that MZ cortical interneurons undergo a second phase of tangential migration in all directions and over long distances, after reaching the cortex by dorsomedial tangential Migration.
Abstract: Most GABAergic interneurons originate from the basal forebrain and migrate tangentially into the cortex. The migratory pathways and mode of interneuron migration within the developing cerebral cortex, however, previously was largely unknown. Time-lapse imaging and in vivo labelling with glutamate decarboxylase (GAD)67-green fluorescence protein (GFP) knock-in embryonic mice with expression of GFP in gamma-aminobutyric acid (GABA)ergic neurons indicated that multidirectional tangential (MDT) migration of interneurons takes place in both the marginal zone (MZ) and the ventricular zone (VZ) of the cortex. Quantitative analysis of migrating interneurons showed that rostrocaudally migrating neurons outnumber those migrating mediolaterally in both of these zones. In vivo labelling with a lipophilic dye showed that the MDT migration in the MZ occurs throughout the cortex over distances of up to 3 mm during a period of a few days. These results indicate that MZ cortical interneurons undergo a second phase of tangential migration in all directions and over long distances, after reaching the cortex by dorsomedial tangential migration. The MDT migration in the MZ may disperse and intermix interneurons within the cortex, resulting in a balanced distribution of interneuron subtypes.