scholarly journals The Roles of Somatostatin-Expressing (GIN) and Fast-Spiking Inhibitory Interneurons in up-down States of Mouse Neocortex

2010 ◽  
Vol 104 (2) ◽  
pp. 596-606 ◽  
Author(s):  
Erika E. Fanselow ◽  
Barry W. Connors

The neocortex contains multiple types of inhibitory neurons whose properties suggest they may play different roles within the cortical circuit. By recording from three cell types during two distinct network states (up and down states) in vitro, we were able to quantify differences in firing characteristics between these cells during different network regimes. We recorded from regular-spiking (RS) excitatory cells and two types of inhibitory neurons, the fast-spiking (FS) neurons and GFP- (and somatostatin-) expressing inhibitory neurons (GIN), in layer 2/3 of slices from mouse somatosensory neocortex. Comparisons of firing characteristics between these cells during up- and down-states showed several patterns. First, of these cell types, only GIN cells fired persistently during down-states, whereas all three cell types fired readily during up-states. Second, the onset of firing and distribution of action potentials throughout up-states differed by cell type, showing that FS cell up-state firing occurred preferentially near the beginning of the up-state, whereas the firing of RS cells was slower to develop at the start of the up-state, and GIN cell firing was sustained throughout the duration of the up-state. Finally, membrane potential and spike correlations between heterogeneous cell types were more pronounced during up-states and, in the case of RS synapses onto GIN cells, varied throughout the up-state. These results suggest that there is a division of labor between FS and GIN cells as the up-state progresses and suggest that GIN cells could be important in the termination of up-states.

Author(s):  
Hannah Bos ◽  
Anne-Marie Oswald ◽  
Brent Doiron

AbstractSynaptic inhibition is the mechanistic backbone of a suite of cortical functions, not the least of which is maintaining overall network stability as well as modulating neuronal gain. Past cortical models have assumed simplified recurrent networks in which all inhibitory neurons are lumped into a single effective pool. In such models the mechanics of inhibitory stabilization and gain control are tightly linked in opposition to one another – meaning high gain coincides with low stability and vice versa. This tethering of stability and response gain restricts the possible operative regimes of the network. However, it is now well known that cortical inhibition is very diverse, with molecularly distinguished cell classes having distinct positions within the cortical circuit. In this study, we analyze populations of spiking neuron models and associated mean-field theories capturing circuits with pyramidal neurons as well as parvalbumin (PV) and somatostatin (SOM) expressing interneurons. Our study outlines arguments for a division of labor within the full cortical circuit where PV interneurons are ideally positioned to stabilize network activity, whereas SOM interneurons serve to modulate pyramidal cell gain. This segregation of inhibitory function supports stable cortical dynamics over a large range of modulation states. Our study offers a blueprint for how to relate the circuit structure of cortical networks with diverse cell types to the underlying population dynamics and stimulus response.


2020 ◽  
Author(s):  
Xiaoyang Long ◽  
Calvin K. Young ◽  
Sheng-Jia Zhang

AbstractHead direction (HD) information is intricately linked to spatial navigation and cognition. We recently reported the co-existence of all currently recognized spatial cell types can be found in the hindlimb primary somatosensory cortex (S1HL). In this study, we carried out an in-depth characterization of HD cells in S1HL. We show fast-spiking (FS), putative inhibitory neurons are over-represented in and sharply tuned to HD compared to regular-spiking (RS), putative excitatory neurons. These FS HD cells are non-conjunctive, rarely theta modulated, not locally connected and are enriched in layer 4/5a. Their co-existence with RS HD cells and angular head velocity (AHV) cells in a layer-specific fashion through the S1HL presents a previously unreported organization of spatial circuits. These findings challenge the notion that FS, putative inhibitory interneurons are weakly tuned to external stimuli in general and present a novel local network configuration not reported in other parts of the brain.


2009 ◽  
Vol 101 (2) ◽  
pp. 1056-1072 ◽  
Author(s):  
T. Tateno ◽  
H.P.C. Robinson

Quantitative understanding of the dynamics of particular cell types when responding to complex, natural inputs is an important prerequisite for understanding the operation of the cortical network. Different types of inhibitory neurons are connected by electrical synapses to nearby neurons of the same type, enabling the formation of synchronized assemblies of neurons with distinct dynamical behaviors. Under what conditions is spike timing in such cells determined by their intrinsic dynamics and when is it driven by the timing of external input? In this study, we have addressed this question using a systematic approach to characterizing the input–output relationships of three types of cortical interneurons (fast spiking [FS], low-threshold spiking [LTS], and nonpyramidal regular-spiking [NPRS] cells) in the rat somatosensory cortex, during fluctuating conductance input designed to mimic natural complex activity. We measured the shape of average conductance input trajectories preceding spikes and fitted a two-component linear model of neuronal responses, which included an autoregressive term from its own output, to gain insight into the input–output relationships of neurons. This clearly separated the contributions of stimulus and discharge history, in a cell-type dependent manner. Unlike LTS and NPRS cells, FS cells showed a remarkable switch in dynamics, from intrinsically driven spike timing to input-fluctuation–controlled spike timing, with the addition of even a small amount of inhibitory conductance. Such a switch could play a pivotal role in the function of FS cells in organizing coherent gamma oscillations in the local cortical network. Using both pharmacological perturbations and modeling, we show how this property is a consequence of the particular complement of voltage-dependent conductances in these cells.


1985 ◽  
Vol 54 (4) ◽  
pp. 782-806 ◽  
Author(s):  
D. A. McCormick ◽  
B. W. Connors ◽  
J. W. Lighthall ◽  
D. A. Prince

Slices of sensorimotor and anterior cingulate cortex from guinea pigs were maintained in vitro and bathed in a normal physiological medium. Electrophysiological properties of neurons were assessed with intracellular recording techniques. Some neurons were identified morphologically by intracellular injection of the fluorescent dye Lucifer yellow CH. Three distinct neuronal classes of electrophysiological behavior were observed; these were termed regular spiking, bursting, and fast spiking. The physiological properties of neurons from sensorimotor and anterior cingulate areas did not differ significantly. Regular-spiking cells were characterized by action potentials with a mean duration of 0.80 ms at one-half amplitude, a ratio of maximum rate of spike rise to maximum rate of fall of 4.12, and a prominent afterhyperpolarization following a train of spikes. The primary slope of initial spike frequency versus injected current intensity was 241 Hz/nA. During prolonged suprathreshold current pulses the frequency of firing adapted strongly. When local synaptic pathways were activated, all cells were transiently excited and then strongly inhibited. Bursting cells were distinguished by their ability to generate endogenous, all-or-none bursts of three to five action potentials. Their properties were otherwise very similar to regular-spiking cells. The ability to generate a burst was eliminated when the membrane was depolarized to near the firing threshold with tonic current. By contrast, hyperpolarization of regular-spiking (i.e., nonbursting) cells did not uncover latent bursting tendencies. The action potentials of fast-spiking cells were much briefer (mean of 0.32 ms) than those of the other cell types.(ABSTRACT TRUNCATED AT 250 WORDS)


2005 ◽  
Vol 94 (2) ◽  
pp. 1509-1518 ◽  
Author(s):  
Horacio G. Rotstein ◽  
Dmitri D. Pervouchine ◽  
Corey D. Acker ◽  
Martin J. Gillies ◽  
John A. White ◽  
...  

The oriens-lacunosum moleculare (O-LM) subtype of interneuron is a key component in the formation of the theta rhythm (8–12 Hz) in the hippocampus. It is known that the CA1 region of the hippocampus can produce theta rhythms in vitro with all ionotropic excitation blocked, but the mechanisms by which this rhythmicity happens were previously unknown. Here we present a model suggesting that individual O-LM cells, by themselves, are capable of producing a single-cell theta-frequency firing, but coupled O-LM cells are not capable of producing a coherent population theta. By including in the model fast-spiking (FS) interneurons, which give rise to IPSPs that decay faster than those of the O-LM cells, coherent theta rhythms are produced. The inhibition to O-LM cells from the FS cells synchronizes the O-LM cells, but only when the FS cells themselves fire at a theta frequency. Reciprocal connections from the O-LM cells to the FS cells serve to parse the FS cell firing into theta bursts, which can then synchronize the O-LM cells. A component of the model O-LM cell critical to the synchronization mechanism is the hyperpolarization-activated h-current. The model can robustly reproduce relative phases of theta frequency activity in O-LM and FS cells.


2013 ◽  
Vol 109 (5) ◽  
pp. 1296-1306 ◽  
Author(s):  
Jokūbas Žiburkus ◽  
John R. Cressman ◽  
Steven J. Schiff

Precisely timed and dynamically balanced excitatory (E) and inhibitory (I) conductances underlie the basis of neural network activity. Normal E/I balance is often shifted in epilepsy, resulting in neuronal network hyperexcitability and recurrent seizures. However, dynamics of the actual excitatory and inhibitory synaptic conductances ( ge and gi, respectively) during seizures remain unknown. To study the dynamics of E and I network balance, we calculated ge and gi during the initiation, body, and termination of seizure-like events (SLEs) in the rat hippocampus in vitro. Repetitive emergent SLEs in 4-aminopyridine (100 μM) and reduced extracellular magnesium (0.6 mM) were recorded in the identified CA1 pyramidal cells (PC) and oriens-lacunosum moleculare (O-LM) interneurons. Calculated ge/ gi ratio dynamics showed that the initiation stage of the SLEs was dominated by inhibition in the PCs and was more balanced in the O-LM cells. During the body of the SLEs, the balance shifted toward excitation, with ge and gi peaking in both cell types at nearly the same time. In the termination phase, PCs were again dominated by inhibition, whereas O-LM cells experienced persistent excitatory synaptic barrage. In this way, increased excitability of interneurons may play roles in both seizure initiation (Žiburkus J, Cressman JR, Barreto E, Schiff SJ. J Neurophysiol 95: 3948–3954, 2006) and in their termination. Overall, SLE stages can be characterized in PC and O-LM cells by dynamically distinct changes in the balance of ge and gi, where a temporal sequence of imbalance shifts with the changing firing patterns of the cellular subtypes comprising the hyperexcitable microcircuits.


2021 ◽  
Vol 23 (1) ◽  
pp. 202
Author(s):  
Estilla Zsófia Tóth ◽  
Felicia Gyöngyvér Szabó ◽  
Ágnes Kandrács ◽  
Noémi Orsolya Molnár ◽  
Gábor Nagy ◽  
...  

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated—in conjunction with the electron microscopy—that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.


Author(s):  
K. Shankar Narayan ◽  
Kailash C. Gupta ◽  
Tohru Okigaki

The biological effects of short-wave ultraviolet light has generally been described in terms of changes in cell growth or survival rates and production of chromosomal aberrations. Ultrastructural changes following exposure of cells to ultraviolet light, particularly at 265 nm, have not been reported.We have developed a means of irradiating populations of cells grown in vitro to a monochromatic ultraviolet laser beam at a wavelength of 265 nm based on the method of Johnson. The cell types studies were: i) WI-38, a human diploid fibroblast; ii) CMP, a human adenocarcinoma cell line; and iii) Don C-II, a Chinese hamster fibroblast cell strain. The cells were exposed either in situ or in suspension to the ultraviolet laser (UVL) beam. Irradiated cell populations were studied either "immediately" or following growth for 1-8 days after irradiation.Differential sensitivity, as measured by survival rates were observed in the three cell types studied. Pattern of ultrastructural changes were also different in the three cell types.


Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).


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