scholarly journals Properties of a Population of GABAergic Cells in Murine Auditory Cortex Weakly Excited by Thalamic Stimulation

2006 ◽  
Vol 96 (6) ◽  
pp. 3194-3208 ◽  
Author(s):  
Yakov I. Verbny ◽  
Ferenc Erdélyi ◽  
Gábor Szabó ◽  
Matthew I. Banks
Keyword(s):  
Auditory Cortex ◽  
Fluorescent Protein ◽  
Receptive Fields ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Dendritic Morphology ◽  
Acid Decarboxylase ◽  
Thalamic Stimulation ◽  
Medial Geniculate ◽  
Feedforward Inhibition

Feedforward inhibition triggered by thalamocortical (TC) afferents sharpens onset responses and shapes receptive fields of pyramidal cells in auditory cortex (ACx). Previous studies focused only on interneurons located in and around layer IV in primary ACx, target of the dense thalamic projections from ventral medial geniculate. We investigated a population of feedforward interneurons located throughout layers I–V and activated by both afferents from primary and nonprimary thalamus using recordings from auditory TC brain slices obtained from mice expressing green fluorescent protein under control of the glutamic acid decarboxylase (GAD65) promoter in a subpopulation of cortical GABAergic cells. We studied the responses of these interneurons and of pyramidal cells in ACx to thalamic stimulation and to hyper- and depolarizing current pulses. Most interneurons exhibited monosynaptic responses to thalamic stimulation, but this excitation was weak and subthreshold. Interneurons had multipolar dendritic morphology with widespread and dense axonal projections extending several hundred micrometers from the soma. In pyramidal cells from layers II–IV, thalamic excitatory postsynaptic potentials were significantly larger than in interneurons and were superthreshold in 40% of cells, but in these cells, there was no evidence of feedforward inhibition. By contrast, feedforward inhibition was observed in 12 of 18 layer V pyramidal cells. Thus feedforward inhibition in supragranular layers of ACx is weak, and these interneurons require coincident excitation to be activated by thalamic inputs.

Anatomic, Intrinsic, and Synaptic Properties of Dorsal and Ventral Division Neurons in Rat Medial Geniculate Body

1999 ◽  
Vol 81 (5) ◽  
pp. 1999-2016 ◽  
Author(s):  
Edward L. Bartlett ◽  
Philip H. Smith
Keyword(s):  
Membrane Potential ◽  
Nmda Receptors ◽  
Brain Slices ◽  
Medial Geniculate Body ◽  
Dendritic Tree ◽  
Dendritic Morphology ◽  
Thalamic Reticular Nucleus ◽  
Membrane Properties ◽  
Reticular Nucleus ◽  
Medial Geniculate

Anatomic, intrinsic, and synaptic properties of dorsal and ventral division neurons in rat medial geniculate body. Presently little is known about what basic synaptic and cellular mechanisms are employed by thalamocortical neurons in the two main divisions of the auditory thalamus to elicit their distinct responses to sound. Using intracellular recording and labeling methods, we characterized anatomic features, membrane properties, and synaptic inputs of thalamocortical neurons in the dorsal (MGD) and ventral (MGV) divisions in brain slices of rat medial geniculate body. Quantitative analysis of dendritic morphology demonstrated that tufted neurons in both divisions had shorter dendrites, smaller dendritic tree areas, more profuse branching, and a greater dendritic polarization compared with stellate neurons, which were only found in MGD. Tufted neuron dendritic polarization was not as strong or consistent as earlier Golgi studies suggested. MGV and MGD cells had similar intrinsic properties except for an increased prevalence of a depolarizing sag potential in MGV neurons. The sag was the only intrinsic property correlated with cell morphology, seen only in tufted neurons in either division. Many MGV and MGD neurons received excitatory and inhibitory inferior colliculus (IC) inputs (designated IN/EX or EX/IN depending on excitation/inhibition sequence). However, a significant number only received excitatory inputs (EX/O) and a few only inhibitory (IN/O). Both MGV and MGD cells displayed similar proportions of response combinations, but suprathreshold EX/O responses only were observed in tufted neurons. Excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) had multiple distinguishable amplitude levels implying convergence. Excitatory inputs activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors the relative contributions of which were variable. For IN/EX cells with suprathreshold inputs, first-spike timing was independent of membrane potential unlike that of EX/O cells. Stimulation of corticothalamic (CT) and thalamic reticular nucleus (TRN) axons evoked a GABAA IPSP, EPSP, GABAB IPSP sequence in most neurons with both morphologies in both divisions. TRN IPSPs and CT EPSPs were graded in amplitude, again suggesting convergence. CT inputs activated AMPA and NMDA receptors. The NMDA component of both IC and CT inputs had an unusual voltage dependence with a detectable dl-2-amino-5-phosphonovaleric acid-sensitive component even below −70 mV. First-spike latencies of CT evoked action potentials were sensitive to membrane potential regardless of whether the TRN IPSP was present. Overall, our in vitro data indicate that reported regional differences in the in vivo responses of MGV and MGD cells to auditory stimuli are not well correlated with major differences in intrinsic membrane features or synaptic responses between cell types.

scholarly journals Electrophysiological properties of genetically identified subtypes of layer 5 neocortical pyramidal neurons: Ca2+ dependence and differential modulation by norepinephrine

2015 ◽  
Vol 113 (7) ◽  
pp. 2014-2032 ◽  
Author(s):  
Dongxu Guan ◽  
William E. Armstrong ◽  
Robert C. Foehring
Keyword(s):  
Pyramidal Neurons ◽  
Fluorescent Protein ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Field Size ◽  
Repetitive Firing ◽  
Differential Modulation ◽  
Electrophysiological Properties ◽  
Laminar Distribution ◽  
Neocortical Pyramidal Neurons

We studied neocortical pyramidal neurons from two lines of bacterial artificial chromosome mice ( etv1 and glt; Gene Expression Nervous System Atlas: GENSAT project), each of which expresses enhanced green fluorescent protein (EGFP) in a different subpopulation of layer 5 pyramidal neurons. In barrel cortex, etv1 and glt pyramidal cells were previously reported to differ in terms of their laminar distribution, morphology, thalamic inputs, cellular targets, and receptive field size. In this study, we measured the laminar distribution of etv1 and glt cells. On average, glt cells were located more deeply; however, the distributions of etv1 and glt cells extensively overlap in layer 5. To test whether these two cell types differed in electrophysiological properties that influence firing behavior, we prepared acute brain slices from 2–4-wk-old mice, where EGFP-positive cells in somatosensory cortex were identified under epifluorescence and then studied using whole cell current- or voltage-clamp recordings. We studied the details of action potential parameters and repetitive firing, characterized by the larger slow afterhyperpolarizations (AHPs) in etv1 neurons and larger medium AHPs (mAHPS) in glt cells, and compared currents underlying the mAHP and slow AHP (sAHP) in etv1 and glt neurons. Etv1 cells exhibited lower d V/d t for spike polarization and repolarization and reduced direct current (DC) gain (lower f- I slope) for repetitive firing than glt cells. Most importantly, we found that 1) differences in the expression of Ca2+-dependent K+ conductances (small-conductance calcium-activated potassium channels and sAHP channels) determine major functional differences between etv1 and glt cells, and 2) there is differential modulation of etv1 and glt neurons by norepinephrine.

Co-Transmission of Dopamine and GABA in Periglomerular Cells

2008 ◽  
Vol 99 (3) ◽  
pp. 1559-1564 ◽  
Author(s):  
Brady J. Maher ◽  
Gary L. Westbrook
Keyword(s):  
Receptor Antagonist ◽  
Fluorescent Protein ◽  
D2 Receptor ◽  
Brain Slices ◽  
Olfactory Receptor Neuron ◽  
Afferent Input ◽  
Acid Decarboxylase ◽  
Calcium Dependent ◽  
Green Fluorescent ◽  
Periglomerular Cells

Most central neurons package and release a single transmitter. However co-transmission of fast-acting and modulatory transmitters has been observed in vertebrate and invertebrate systems. Here we describe a population of periglomerular cells in mouse brain slices (PND14-21) that co-release dopamine and GABA. We made whole cell recordings from periglomerular cells that expressed enhanced green fluorescent protein (EGFP) under the control of the tyrosine hyrdoxylase (TH) promoter. Immunolabeling confirmed that EGFP+ periglomerular cells synthesized TH as well as glutamic acid decarboxylase (GAD). Stimulation of olfactory receptor neuron (ORN) afferent input evoked excitatory postsynaptic currents (EPSCs) in EGFP+ cells that were inhibited by cocaine, which blocks dopamine transport. These effects were reversed by the D2 receptor antagonist sulpiride. Cocaine also increased the paired-pulse ratio of ORN-evoked EPSCs. These results demonstrate that TH+ periglomerular cells spontaneously release dopamine. In addition to dopamine, TH-EGFP+ cells also released GABA. Brief depolarizing voltage steps in labeled cells evoked a tail current that was completely blocked by the GABAA receptor antagonist gabazine and by cadmium, indicative of calcium-dependent self-inhibition in periglomerular cells. However, similar voltage steps were insufficient to cause D2-receptor mediated inhibition of ORN terminals. Our results indicate that TH+ periglomerular cells are directly activated by ORN input and release both dopamine and GABA. We suggest that concerted activation of multiple periglomerular cells may be required to detect dopamine release under normal physiological conditions.

scholarly journals Cell Type–Specific GABAA Receptor–Mediated Tonic Inhibition in Mouse Neocortex

2008 ◽  
Vol 100 (1) ◽  
pp. 526-532 ◽  
Author(s):  
Irina Vardya ◽  
Kim R. Drasbek ◽  
Zita Dósa ◽  
Kimmo Jensen
Keyword(s):  
Fluorescent Protein ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Tonic Inhibition ◽  
Synaptic Activity ◽  
Inhibitory Input ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific ◽  
Green Fluorescent

Activity of extrasynaptic GABAA receptors mediating tonic inhibition is thought to play an important role for the excitability of the mammalian cerebral cortex. However, little is known about the cell type–specific expression of tonic inhibition in particular types of cortical interneurons. Here, we used transgenic mice expressing green fluorescent protein (GFP) in somatostatin-positive (SOM) interneurons and investigated tonic inhibition in SOM interneurons versus pyramidal cells in neocortical layers 2/3. In brain slices, pyramidal cells showed a tonic current of 66 ± 19 pA in response to the δ-subunit selective GABAA agonist THIP (1 μM). On the other hand, tonic inhibition was absent in SOM interneurons (8 ± 1 pA) in response to THIP. As opposed to pyramidal cells, SOM interneurons were also insensitive to the δ-subunit preferring neurosteroid allotetrahydrodeoxycorticosterone (THDOC) (100 nM) and to elevated endogenous GABA levels in the slice. Finally, SOM interneurons received only 45% of the phasic charge transfer during GABAA receptor–mediated synaptic activity compared with pyramidal cells. Altogether, our study indicates that SOM interneurons receive relatively weak inhibitory input and cannot be brought under the influence of tonic inhibition.

scholarly journals Competition and convergence between auditory and cross-modal visual inputs to primary auditory cortical areas

2011 ◽  
Vol 105 (4) ◽  
pp. 1558-1573 ◽  
Author(s):  
Yu-Ting Mao ◽  
Tian-Miao Hua ◽  
Sarah L. Pallas
Keyword(s):  
Auditory Cortex ◽  
Multisensory Processing ◽  
Sensory Deprivation ◽  
Target Space ◽  
Target Cells ◽  
Auditory Input ◽  
Visual Neurons ◽  
Cortical Areas ◽  
Visual Inputs ◽  
Medial Geniculate

Sensory neocortex is capable of considerable plasticity after sensory deprivation or damage to input pathways, especially early in development. Although plasticity can often be restorative, sometimes novel, ectopic inputs invade the affected cortical area. Invading inputs from other sensory modalities may compromise the original function or even take over, imposing a new function and preventing recovery. Using ferrets whose retinal axons were rerouted into auditory thalamus at birth, we were able to examine the effect of varying the degree of ectopic, cross-modal input on reorganization of developing auditory cortex. In particular, we assayed whether the invading visual inputs and the existing auditory inputs competed for or shared postsynaptic targets and whether the convergence of input modalities would induce multisensory processing. We demonstrate that although the cross-modal inputs create new visual neurons in auditory cortex, some auditory processing remains. The degree of damage to auditory input to the medial geniculate nucleus was directly related to the proportion of visual neurons in auditory cortex, suggesting that the visual and residual auditory inputs compete for cortical territory. Visual neurons were not segregated from auditory neurons but shared target space even on individual target cells, substantially increasing the proportion of multisensory neurons. Thus spatial convergence of visual and auditory input modalities may be sufficient to expand multisensory representations. Together these findings argue that early, patterned visual activity does not drive segregation of visual and auditory afferents and suggest that auditory function might be compromised by converging visual inputs. These results indicate possible ways in which multisensory cortical areas may form during development and evolution. They also suggest that rehabilitative strategies designed to promote recovery of function after sensory deprivation or damage need to take into account that sensory cortex may become substantially more multisensory after alteration of its input during development.

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

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

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

scholarly journals A New Transgenic Mouse Line for Imaging Mitochondrial Calcium Signals

Function ◽  
2021 ◽  
Vol 2 (3) ◽  
Author(s):  
Nelly Redolfi ◽  
Elisa Greotti ◽  
Giulia Zanetti ◽  
Tino Hochepied ◽  
Cristina Fasolato ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Fluorescent Protein ◽  
Ex Vivo ◽  
Brain Slices ◽  
Resonance Energy ◽  
Mouse Line ◽  
Isolated Cells ◽  
Genomic Locus ◽  
Transgenic Mouse Line

AbstractMitochondria play a key role in cellular calcium (Ca2+) homeostasis. Dysfunction in the organelle Ca2+ handling appears to be involved in several pathological conditions, ranging from neurodegenerative diseases, cardiac failure and malignant transformation. In the past years, several targeted green fluorescent protein (GFP)-based genetically encoded Ca2+ indicators (GECIs) have been developed to study Ca2+ dynamics inside mitochondria of living cells. Surprisingly, while there is a number of transgenic mice expressing different types of cytosolic GECIs, few examples are available expressing mitochondria-localized GECIs, and none of them exhibits adequate spatial resolution. Here we report the generation and characterization of a transgenic mouse line (hereafter called mt-Cam) for the controlled expression of a mitochondria-targeted, Förster resonance energy transfer (FRET)-based Cameleon, 4mtD3cpv. To achieve this goal, we engineered the mouse ROSA26 genomic locus by inserting the optimized sequence of 4mtD3cpv, preceded by a loxP-STOP-loxP sequence. The probe can be readily expressed in a tissue-specific manner upon Cre recombinase-mediated excision, obtainable with a single cross. Upon ubiquitous Cre expression, the Cameleon is specifically localized in the mitochondrial matrix of cells in all the organs and tissues analyzed, from embryos to aged animals. Ca2+ imaging experiments performed in vitro and ex vivo in brain slices confirmed the functionality of the probe in isolated cells and live tissues. This new transgenic mouse line allows the study of mitochondrial Ca2+ dynamics in different tissues with no invasive intervention (such as viral infection or electroporation), potentially allowing simple calibration of the fluorescent signals in terms of mitochondrial Ca2+ concentration ([Ca2+]).

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