Similar Inhibitory Processes Dominate the Responses of Cat Lateral Amygdaloid Projection Neurons to Their Various Afferents

1997 ◽  
Vol 77 (1) ◽  
pp. 341-352 ◽  
Author(s):  
E. J. Lang ◽  
D. Paré

Lang, E. J. and D. Paré. Similar inhibitory processes dominate the responses of cat lateral amygdaloid projection neurons to their various afferents. J. Neurophysiol. 77: 341–352, 1997. To investigate the impact of inhibitory processes on responses of lateral amygdaloid (LAT) neurons, intracellular recordings were obtained from identified LAT projection neurons in barbiturate-anesthetized cats. Synaptic responses evoked by perirhinal (PRH), entorhinal (ENT), basomedial, and LAT stimulation were investigated. Regardless of stimulation site, responses consisted of an excitatory postsynaptic potential (EPSP) that either preceded and was truncated by an inhibitory postsynaptic potential (IPSP) or occurred just after the IPSP onset. IPSPs were monophasic, lasted hundreds of milliseconds, and were of such large amplitude and rapid onset that they effectively opposed the EPSPs, generally preventing orthodromic spikes. All sites elicited IPSPs with relatively negative reversal potentials around −85 mV. Experiments analyzing the underlying ionic mechanisms are presented in the companion paper. Evoked responses were similar to synaptic potentials associated with spontaneous EEG events, known as simple (small, monophasic) and complex (large, triphasic) ENT sharp potentials (SPs), with no difference between the reversals of evoked and SP-related IPSPs (−83.2 ± 2.7 mV). IPSPs coinciding with complex SPs truncated SP-related EPSPs more rapidly and had larger amplitudes and longer durations than those related to simple SPs. These differences reflected the fact that the amplitude and duration of SP-related IPSPs were correlated with SP amplitude. Similar variations were reproduced in evoked IPSPs by varying the stimulus intensity. Low intensities generated predominantly excitatory responses consisting of EPSPs sometimes followed by small IPSPs, whereas high intensities evoked predominantly inhibitory responses comprised of a large IPSP that truncated or occluded the EPSPs. Orthodromic spikes were elicited only in a narrow range of intermediate intensities. These changes in the evoked response primarily reflected increases in the IPSP evoked at high intensities. PRH stimulation at different rostro-caudal levels demonstrated that rostral sites elicited larger EPSPs and IPSPs with shorter latencies and longer durations than caudal sites. These differences probably reflect contrasting patterns of activity spread through the PRH cortex, suggesting that the intact cortical circuitry allowed a temporally distributed activation of inhibitory interneurons and thereby partly explains the long duration and monophasic nature of the IPSPs. Inhibition, thus, plays a primary role in shaping LAT neuronal responses. The profuse intrinsic connectivity of the LAT nucleus and parahippocampal cortices may underlie the relatively invariant response pattern of LAT neurons and suggests a common mode of information processing, based upon quantitative, rather than qualitative, differences in activation of LAT circuitry. Therefore we propose that effective transmission of signals through the LAT nucleus may require activation of specifically sized neuronal ensembles, rather than widespread afferent excitation.

2017 ◽  
Author(s):  
Arielle L. Baker ◽  
Ryan J. O’Toole ◽  
Allan T. Gulledge

AbstractPyramidal neurons in layer 5 of the neocortex comprise two broad classes of projection neurons: corticofugal neurons, including corticopontine (CPn) neurons, and intratelencephalic neurons, including commissural/callosal (COM) neurons. These non-overlapping neuron subpopulations represent discrete cortical output channels contributing to perception, decision making, and behavior. CPn and COM neurons have distinct morphological and physiological characteristics, and divergent responses to modulatory transmitters such as serotonin and acetylcholine (ACh). To better understand how ACh regulates cortical output, in slices of mouse prefrontal cortex (PFC) we compared the responsivity of CPn and COM neurons to transient exposure to exogenous or endogenous ACh. In both neuron subtypes, exogenous ACh generated qualitatively similar biphasic responses in which brief hyperpolarization was followed by longer-lasting enhancement of excitability. However, cholinergic inhibition was more pronounced in COM neurons, while excitatory responses were larger and longer lasting in CPn neurons. Similarly, optically triggered release of endogenous ACh from cholinergic terminals preferentially and persistently (for ~40 s) enhanced the excitability of CPn neurons, but had little impact on COM neurons. Cholinergic excitation of CPn neurons involved at least three distinct ionic mechanisms: activation of a calcium-sensitive but calcium-permeable nonspecific cation conductance, suppression of Kv7 channels (the “M-current”), and activation of the calcium-dependent nonspecific cation conductance underlying afterdepolarizations. Our results demonstrate projection-specific selectivity in cholinergic signaling in the PFC, and suggest that transient release of ACh during behavior will preferentially promote corticofugal output.


2021 ◽  
Vol 15 ◽  
Author(s):  
Adeel A. Memon ◽  
Micah E. Bagley ◽  
Rose B. Creed ◽  
Amy W. Amara ◽  
Matthew S. Goldberg ◽  
...  

Loss of function mutations in PARK6, the gene that encodes the protein PTEN-induced kinase 1 (PINK1), cause autosomal recessive familial Parkinson’s disease (PD). While PD is clinically diagnosed by its motor symptoms, recent studies point to the impact of non-motor symptoms, including cognitive dysfunction in the early pre-motor stages of the disease (Aarsland et al., 2004; Chaudhuri and Schapira, 2009). As the hippocampus is a key structure for learning and memory, this study aimed to determine whether synaptic transmission is affected at CA3-CA1 excitatory synapses in PINK1 knockout rats at an age when we recently reported a gain of function at excitatory synapses onto spiny projection neurons in the dorsal striatum (Creed et al., 2020) and when motor symptoms are beginning to appear (Dave et al., 2014). Using extracellular dendritic field excitatory postsynaptic potential recordings at CA3-CA1 synapses in dorsal hippocampus 4-to 5- month old PINK1 KO rats and wild-type littermate controls, we observed no detectable differences in the strength of basal synaptic transmission, paired-pulse facilitation, or long-term potentiation. Our results suggest that loss of PINK1 protein does not cause a general dysfunction of excitatory transmission throughout the brain at this young adult age when excitatory transmission is abnormal in the striatum.


1997 ◽  
Vol 77 (1) ◽  
pp. 353-363 ◽  
Author(s):  
E. J. Lang ◽  
D. Paré

Lang, E. J. and D. Paré. Synaptic and synaptically activated intrinsic conductances underlie inhibitory potentials in cat lateral amygdaloid projection neurons in vivo. J. Neurophysiol. 77: 353–363, 1997. The companion paper demonstrated that the responses of lateral amygdaloid (LAT) projection neurons to the stimulation of major input and output structures are dominated by monophasic hyperpolarizing potentials of large amplitude. To characterize the mechanisms underlying these inhibitory potentials, intracellular recordings of cortically evoked responses were obtained from morphologically and/or physiologically identified LAT projection neurons in barbiturate anesthetized cats. The reversal potential of the cortically evoked hyperpolarization was measured at its peak, and 115 ms later (tail), an interval corresponding to the peak latency of the γ-aminobuturic acid-B (GABAB) response previously recorded in vitro. When recorded with K-acetate (KAc) pipettes, these reversal potentials were −86.9 ± 1.6 mV (peak; mean ± SE) and −90.7 ± 1.7 mV (tail), suggesting that both Cl− and K+ conductances contribute throughout the cortically evoked hyperpolarization. The small, but consistent, difference between the two reversal potentials suggested that an additional slowly activating K+-mediated component contributed to the inhibitory postsynaptic potential (IPSP) tail. To determine whether Cl− conductances contributed to the evoked hyperpolarization, recordings were performed with KCl; the peak (−57.8 ± 2.2 mV) and tail (−61.3 ± 2.1 mV) reversal potentials were ∼15–20 mV more depolarized than those recorded with KAc pipettes. However, the difference between the peak and tail reversals remained. In an attempt to block the Cl− conductance, recordings were obtained with pipettes filled with KAc or KCl and 4,4′-diisothiocyanostilbene-2,2′-disulphonic acid (DIDS), a Cl− pump blocker that also was reported to block GABAA responses. With KAc and DIDS, the initial depolarization was prolonged and the amplitude of the hyperpolarization decreased relative to that seen with KAc alone. However, with KCl and DIDS, the reversal potential was shifted to an even greater extent than with KCl pipettes with the evoked response consisting entirely of a large depolarization, which produced a spike burst. These results suggest that LAT neurons have a Cl− pump that is blocked by DIDS, but that their Cl− channels are not blocked by DIDS. To assess the contribution of K+ conductances to cortically evoked hyperpolarizing potentials, recordings were obtained with Cs-acetate pipettes. Under these conditions, the response reversed at more depolarized potentials (peak, −71.9 ± 1.0 mV; tail,−72.0 ± 0.9 mV) compared with KAc recordings, with no difference between the peak and tail reversal potentials. These cells also had depolarized resting potentials (−66.2 ± 1.8 mV) compared with those of cells recorded with KAc pipettes (−73.6 ± 1.8 mV); however, this difference was too small to attribute the shift in reversals to a redistribution of Cl− ions across the membrane. The action potentials generated by LAT neurons under Cs+ had a shoulder that prolonged their falling phase. The increased duration of the spikes was presumably due to a dendritic Ca2+ conductance because LAT amygdaloid neurons are known to possess such conductances and Cs+ blocks the delayed rectifier and some Ca2+-dependent K+ currents. The dramatic reduction of this shoulder by spontaneous and evoked IPSPs suggests that the activation of dendritic conductances by back-propagating somatic action potentials is regulated tightly by synaptic events. Intracellular injection of the Ca2+ chelating agent, 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (100 mM) caused a depolarization of the peak (−75.3 ± 1.3 mV) and tail (−77.7 ± 1.7 mV) reversal potentials during a time course of 15–45 min. Concurrently, the amplitude of the excitatory postsynaptic potential increased whereas that of the hyperpolarization decreased, suggesting that a Ca2+-dependent K+ conductance contributes significantly to the evoked hyperpolarization. In conclusion, the large hyperpolarizing potentials that regulate the excitability of LAT projection neurons appear to be mediated primarily by a Cl−, presumably GABAA, IPSP, and a synaptically activated Ca2+-dependent K+ conductance. A relatively weak K+-mediated, possibly GABAB, IPSP makes a small contribution to the later portions of the response.


1999 ◽  
Vol 202 (10) ◽  
pp. 1301-1309 ◽  
Author(s):  
Y. Sugawara ◽  
K. Grant ◽  
V. Han ◽  
C.C. Bell

In mormyrid electric fish, sensory signals from electroreceptors are relayed to secondary sensory neurons in a cerebellum-like structure known as the electrosensory lateral line lobe (ELL). Efferent neurons and interneurons of the ELL also receive inputs of central origin, including electric organ corollary discharge signals, via parallel fibers and via fibers from the juxtalobar nucleus. To understand the cellular mechanisms of the integration of sensory inputs and central inputs in the ELL, the intracellular activity and ionic properties of the efferent projection neurons and interneurons were examined in an in vitro slice preparation.We focus here on the electrophysiological properties of the efferent neurons of the ELL network, the large fusiform cells and large ganglion cells, and on a class of gamma-aminobutyric acid (GABA)-ergic interneurons known as medium ganglion (MG) cells. In response to current injection through a recording pipette, both types of efferent neuron fire a large narrow spike followed by a large hyperpolarizing afterpotential. The MG cells fire a complex spike which consists of small narrow spikes and a large broad spike. Although the forms of the action potentials in efferent neurons and in MG cells are different, all spikes are mediated by tetrodotoxin (TTX)-sensitive Na+ conductances and spike repolarization is mediated by tetraethylammonium (TEA+)-sensitive K+ conductances. In the presence of TEA+, substitution of Ba2+ for Ca2+ in the bath revealed the presence of a high-voltage-activated Ca2+ conductance.Stimulation of parallel fibers conveying descending input to the ELL molecular layer in vitro evokes an excitatory postsynaptic potential (EPSP), generally followed by an inhibitory postsynaptic potential (IPSP), in the efferent neurons. In MG cells, the same stimulation evokes an EPSP, often followed by a small IPSP. Synaptic transmission at parallel fiber synapses is glutamatergic and is mediated via both N-methyl-d-aspartate (NMDA)- and (AMPA)-type glutamate receptors. The inhibitory component of the parallel fiber response is GABAergic. It is probably mediated via the stellate neurons and the MG cells, which are themselves GABAergic interneurons intrinsic to the ELL network.A hypothetical neural circuit of the intrinsic connections of the ELL, based on the known morphology of projection neurons and medium ganglion interneurons, is presented. This circuit includes an excitatory and an inhibitory submodule. The excitatory submodule is centered on a large fusiform cell and appears to relay the sensory input as a positive ‘ON’ image of an object. The inhibitory submodule is centered on a large ganglion cell and relays a negative ‘OFF’ image to the next higher level. We suggest that MG cells exert an inhibitory bias on efferent neuron types and that the ELL network output is modulated by the dynamically plastic integration of central descending signals with sensory input.


2021 ◽  
Vol 13 (6) ◽  
pp. 3518
Author(s):  
Xiaoyi Xing ◽  
Li Dong ◽  
Cecil Konijnendijk ◽  
Peiyao Hao ◽  
Shuxin Fan ◽  
...  

The spatial variation of poplars’ reproductive phenology in Beijing’s urban area has aggravated the threat of poplar fluff (cotton-like flying seeds) to public health. This research explored the impact of microclimate conditions on the reproductive phenology of female Populus tomentosa in Taoranting Park, a micro-scale green space in Beijing (range <1 km). The observed phenophases covered flowering, fruiting, and seed dispersal, and ENVI-MET was applied to simulate the effect of the microclimate on SGS (start day of the growing season). The results showed that a significant spatial variation in poplar reproductive phenology existed at the research site. The variation was significantly affected by the microclimate factors DMT (daily mean temperature) and DMH (daily mean heat transfer coefficient), with air temperature playing a primary role. Specifically, the phenology of flowering and fruiting phenophases (BBB, BF, FF, FS) was negatively correlated with DMT (−0.983 ≤ r ≤ −0.908, p <0.01) and positively correlated with DMH (0.769 ≤ r ≤ 0.864, p < 0.05). In contrast, DSD (duration of seed dispersal) showed a positive correlation with DMT (r = 0.946, p < 0.01) and a negative correlation with DMH (r = −0.922, p < 0.01). Based on the findings, the increase in air convection with lower air temperature and decrease in microclimate variation in green space can be an effective way to shorten the seed-flying duration to tackle poplar fluff pollution in Beijing’s early spring.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24121-e24121
Author(s):  
Celeste Cagnazzo ◽  
Veronica Franchina ◽  
Giuseppe Toscano ◽  
Franca Fagioli ◽  
Tindara Franchina ◽  
...  

e24121 Background: Barriers for low recruitment in clinical trials have been classified based on three main sources: physician, patient, system. A primary role is played by a low patient awareness, which often leads to a lack of confidence in science and a substantial inability to estimate the benefits deriving from trial participation, aggravated by the spread of fake news. A prospective observational study was conducted to investigate the views of cancer patients on aspects of clinical research, their expectations, the level of comprehensibility of informed consent and the impact of the fake news phenomenon. Methods: From January 2018, after Ethics Committees approval, the ELPIS study was initiated in 9 Italian Medical Oncology Units. After signing the informed consent, patients were asked to complete a questionnaire, consisting of a set of multiple choice and Likert-score questions. Results: As of January 2021, 115 patients were enrolled, with a balanced sex distribution and a prevalence of subjects older than 55-years (79.8%). Regarding the previous knowledge about clinical research, the average score was 3.9 (range 1-5). The vast majority of respondents (91.3%) had already started experimental therapy and many of them constantly used internet (65.2%) and social networks (34.8%). More than half (53.9%) stated the interview with the physician was sufficient for a full understanding of informed consent. In case of doubt, the majority seeked support in the clinician (39.1%) while very few (1.7%) relied on the web. The average score attributed to doctor-patient relationship was equal to 8.89 (range 1-10). Respondents were quite confident in their ability to independently search for information on their disease, discriminate fake news and identify reliable sites (average score 3.26, 3.27, 3.09 respectively, over a range of 1-5). The scores related to the presumed ability to understand the results of a clinical study and to actively collaborate to produce research were high (average score 4.72 and 4.39 over a range of 1-5). Conclusions: Preliminary data from our research show a good level of patient awareness and a fine ability to understand information, discerning real from fake news. Continuing and implementing the training initiatives of the population in the health sector will certainly contribute to further improvement, hopefully obtaining an even greater involvement of patients in the early phases of research.


1984 ◽  
Vol 51 (6) ◽  
pp. 1362-1374 ◽  
Author(s):  
E. Marder ◽  
J. S. Eisen

The two pyloric dilator (PD) motor neurons and the single anterior burster (AB) interneuron are electrically coupled and together comprise the pacemaker for the pyloric central pattern generator of the stomatogastric ganglion of the lobster, Panulirus interruptus. Previous work (31) has shown that the AB neuron is an endogenously bursting neuron, while the PD neuron is a conditional burster. In this paper the effects of physiological inputs and neurotransmitters on isolated PD neurons and AB neurons were studied using the lucifer yellow photoinactivation technique (33). Stimulation of the inferior ventricular nerve (IVN) fibers at high frequencies elicits a triphasic response in AB and PD neurons: a rapid excitatory postsynaptic potential (EPSP) followed by a slow inhibitory postsynaptic potential (IPSP), followed by an enhancement of the pacemaker slow-wave depolarizations. Photoinactivation experiments indicate that the enhancement of the slow wave is due primarily to actions of the IVN fibers on the PD neurons but not on the AB neuron. Bath-applied dopamine dramatically alters the motor output of the pyloric system. Photoinactivation experiments show that 10(-4) M dopamine increases the amplitude and frequency of the slow-wave depolarizations recorded in the AB neurons but hyperpolarizes and inhibits the PD neurons. Bath-applied serotonin increases the frequency and amplitude of the slow-wave depolarizations in the AB neuron but has no effect on PD neurons. Pilocarpine, a muscarinic cholinergic agonist, stimulates slow-wave depolarization production in both PD neurons and the AB neuron, but the waveform and frequency of the slow waves elicited are quite different. These results show that although the electrically coupled PD and AB neurons always depolarize synchronously and act together as the pacemaker for the pyloric system, they respond differently to a neuronal input and to several putative neuromodulators. Thus, despite electrical coupling sufficient to ensure synchronous activity, the PD and AB neurons can be modulated independently.


1988 ◽  
Vol 59 (5) ◽  
pp. 1352-1376 ◽  
Author(s):  
G. F. Tseng ◽  
L. B. Haberly

1. Intracellular recordings were obtained from anatomically verified layer II pyramidal cells in slices from rat piriform cortex cut perpendicular to the surface. 2. Responses to afferent and association fiber stimulation at resting membrane potential consisted of a depolarizing potential followed by a late hyperpolarizing potential (LHP). Membrane polarization by current injection revealed two components in the depolarizing potential: an initial excitatory postsynaptic potential (EPSP) followed at brief latency by an inhibitory postsynaptic potential (IPSP) that inverted with membrane depolarization and truncated the duration of the EPSP. 3. The early IPSP displayed the following characteristics suggesting mediation by gamma-aminobutyric acid (GABA) receptors linked to Cl- channels: associated conductance increase, sensitivity to increases in internal Cl- concentration, blockage by picrotoxin and bicuculline, and potentiation by pentobarbital sodium. The reversal potential was in the depolarizing direction with respect to resting membrane potential so that the inhibitory effect was exclusively via current shunting. 4. The LHP had an associated conductance increase and a reversal potential of -90 mV in normal bathing medium that shifted according to Nernst predictions for a K+ potential with changes in external K+ over the range 4.5-8 mM indicating mediation by the opening of K+ channels and ruling out an electrogenic pump origin. 5. Lack of effect of bath-applied 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) or internally applied ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) on the LHP and failure of high amplitude, direct membrane depolarization to evoke a comparable potential, argue against endogenous mediation of the LHP by a Ca2+ activated K+ conductance [gK(Ca)]. However, an apparent endogenously mediated gK(Ca) with a duration much greater than the LHP was observed in a low percent of layer II pyramidal cells. Lack of effect of 8-Br-cAMP also indicates a lack of dependence of the LHP on cAMP. 6. Other characteristics of the LHP that were demonstrated include: a lack of blockage by GABAA receptor antagonists, a probable voltage sensitivity (decrease in amplitude in the depolarizing direction), and an apparent brief onset latency (less than 10 ms) when the early IPSP was blocked by picrotoxin. The LHP was unaffected by pentobarbital sodium when the early IPSP was blocked by picrotoxin. 7. Both the LHP and early IPSP were blocked by low Ca2+/high Mg2+, consistent with disynaptic mediation.(ABSTRACT TRUNCATED AT 400 WORDS)


1991 ◽  
Vol 65 (5) ◽  
pp. 1055-1066 ◽  
Author(s):  
B. A. Ballyk ◽  
S. J. Quackenbush ◽  
R. D. Andrew

1. Lowered osmolality promotes epileptiform activity both clinically and in the hippocampal slice preparation, but it is unclear how neurons are excited. We studied the effects of altered osmolality on the electrophysiological properties of CA1 pyramidal cells in hippocampal slices by the use of field and intracellular recordings. The excitability of these neurons under various osmotic conditions was gauged by population spike (PS) amplitude, single cell properties, and evoked synaptic input. 2. The orthodromic PS recorded in stratum pyramidale and the field excitatory postsynaptic potential (EPSP) in stratum radiatum were inversely proportional in amplitude to the artificial cerebrospinal fluid (ACSF) osmolality over a range of +/- 80 milliosmoles/kgH2O (mosM). The effect was osmotic because changes occurred within the time frame expected for cellular expansion or shrinkage and because permeable substances such as dimethyl sulfoxide or glycerol were without effect. Dilutional changes in ACSF constituents were experimentally ruled out as promoting excitability. 3. To test whether the field data resulted from a change in single-cell excitability, CA1 cells were intracellularly recorded during exposure to +/- 40 mosM ACSF over 15 min. There was no consistent effect upon CA1 resting potential, cell input resistance, or action potential threshold. 4. Osmotic alteration of orthodromic and antidromic field potentials might involve a change in axonal excitability. However, the evoked afferent volley recorded in CA1 stratum pyramidale or radiatum, which represents the compound action potential (CAP) generated in presynaptic axons, remained osmotically unresponsive with regard to amplitude, duration, or latency. This was also characteristic of CAPs evoked in isolated sciatic and vagus nerve preparations exposed to +/- 80 mosM. Therefore axonal excitability and associated extracellular current flow generated periaxonally are not significantly affected by osmotic shifts. 5. The osmotic effect on field potential amplitudes appeared to be independent of synaptic transmission because the inverse relationship with osmolality held for the antidromically evoked PS. Moreover, as recorded with respect to ground, the intracellular EPSP-inhibitory postsynaptic potential (IPSP) sequence (evoked from CA3 stratum radiatum) was not altered by osmolality. 6. The PS could occasionally be recorded intracellularly as a brief negativity interrupting the evoked EPSP. In hyposmotic ACSF, the amplitude increased and action potentials arose from the trough of the negativity as expected for a field effect. This is presumably the result of enhanced intracellular channeling of current caused by the increased extracellular resistance that accompanies cellular swelling.(ABSTRACT TRUNCATED AT 400 WORDS)


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