scholarly journals Chronic intermittent ethanol promotes ventral subiculum hyperexcitability via increases in extrinsic basolateral amygdala input and local network activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eva C. Bach ◽  
Sarah E. Ewin ◽  
Alexandra D. Baldassaro ◽  
Hannah N. Carlson ◽  
Jeffrey L. Weiner
Keyword(s):  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Ex Vivo ◽  
Excitatory Input ◽  
Ethanol Exposure ◽  
Network Activity ◽  
Local Network ◽  
Affective States ◽  
Chronic Intermittent Ethanol ◽  
Integral Role

AbstractThe hippocampus, particularly its ventral domain, can promote negative affective states (i.e. stress and anxiety) that play an integral role in the development and persistence of alcohol use disorder (AUD). The ventral hippocampus (vHC) receives strong excitatory input from the basolateral amygdala (BLA) and the BLA-vHC projection bidirectionally modulates anxiety-like behaviors. However, no studies have examined the effects of chronic alcohol on the BLA-vHC circuit. In the present study, we used ex vivo electrophysiology in conjunction with optogenetic approaches to examine the effects of chronic intermittent ethanol exposure (CIE), a well-established rodent model of AUD, on the BLA-vHC projection and putative intrinsic vHC synaptic plasticity. We discovered prominent BLA innervation in the subicular region of the vHC (vSub). CIE led to an overall increase in the excitatory/inhibitory balance, an increase in AMPA/NMDA ratios but no change in paired-pulse ratios, consistent with a postsynaptic increase in excitability in the BLA-vSub circuit. CIE treatment also led to an increase in intrinsic network excitability in the vSub. Overall, our findings suggest a hyperexcitable state in BLA-vSub specific inputs as well as intrinsic inputs to vSub pyramidal neurons which may contribute to the negative affective behaviors associated with CIE.

scholarly journals Distinct mechanisms of signal processing by lamina I spino-parabrachial neurons

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
K. Agashkov ◽  
V. Krotov ◽  
M. Krasniakova ◽  
D. Shevchuk ◽  
Y. Andrianov ◽  
...  
Keyword(s):  
Signal Processing ◽  
Ex Vivo ◽  
Network Activity ◽  
Local Network ◽  
Cellular Mechanisms ◽  
Afferent Stimulation ◽  
Lamina I ◽  
C Fiber ◽  
Nociceptive Input ◽  
High Output

AbstractLamina I spino-parabrachial neurons (SPNs) receive peripheral nociceptive input, process it and transmit to the supraspinal centres. Although responses of SPNs to cutaneous receptive field stimulations have been intensively studied, the mechanisms of signal processing in these neurons are poorly understood. Therefore, we used an ex-vivo spinal cord preparation to examine synaptic and cellular mechanisms determining specific input-output characteristics of the neurons. The vast majority of the SPNs received a few direct nociceptive C-fiber inputs and generated one spike in response to saturating afferent stimulation, thus functioning as simple transducers of painful stimulus. However, 69% of afferent stimulation-induced action potentials in the entire SPN population originated from a small fraction (19%) of high-output neurons. These neurons received a larger number of direct Aδ- and C-fiber inputs, generated intrinsic bursts and efficiently integrated a local network activity via NMDA-receptor-dependent mechanisms. The high-output SPNs amplified and integrated the nociceptive input gradually encoding its intensity into the number of generated spikes. Thus, different mechanisms of signal processing allow lamina I SPNs to play distinct roles in nociception.

scholarly journals IgSF11 homophilic adhesion proteins promote layer-specific synaptic assembly of the cortical interneuron subtype

2021 ◽  
Vol 7 (29) ◽  
pp. eabf1600
Author(s):  
Yasufumi Hayano ◽  
Yugo Ishino ◽  
Jung Ho Hyun ◽  
Carlos G. Orozco ◽  
André Steinecke ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Cell Types ◽  
Network Activity ◽  
Local Network ◽  
Immunoglobulin Superfamily ◽  
Specific Cell ◽  
Loss Of Function ◽  
Adhesion Proteins ◽  
Homophilic Adhesion

The most prominent structural hallmark of the mammalian neocortical circuitry is the layer-based organization of specific cell types and synaptic inputs. Accordingly, cortical inhibitory interneurons (INs), which shape local network activity, exhibit subtype-specific laminar specificity of synaptic outputs. However, the underlying molecular mechanisms remain unknown. Here, we demonstrate that Immunoglobulin Superfamily member 11 (IgSF11) homophilic adhesion proteins are preferentially expressed in one of the most distinctive IN subtypes, namely, chandelier cells (ChCs) that specifically innervate axon initial segments of pyramidal neurons (PNs), and their synaptic laminar target. Loss-of-function experiments in either ChCs or postsynaptic cells revealed that IgSF11 is required for ChC synaptic development in the target layer. While overexpression of IgSF11 in ChCs enlarges ChC presynaptic boutons, expressing IgSF11 in nontarget layers induces ectopic ChC synapses. These findings provide evidence that synapse-promoting adhesion proteins, highly localized to synaptic partners, determine the layer-specific synaptic connectivity of the cortical IN subtype.

scholarly journals Withdrawal from Chronic Ethanol Exposure Increases Postsynaptic Glutamate Function of Insular Cortex Projections to the Rat Basolateral Amygdala

2019 ◽  
Author(s):  
Molly M. McGinnis ◽  
Brian C. Parrish ◽  
Brian A. McCool
Keyword(s):  
Synaptic Plasticity ◽  
Negative Affect ◽  
Basolateral Amygdala ◽  
Glutamate Release ◽  
Insular Cortex ◽  
Ethanol Exposure ◽  
Ethanol Withdrawal ◽  
Chronic Ethanol ◽  
Chronic Ethanol Exposure ◽  
Chronic Intermittent Ethanol

AbstractA key feature of alcohol use disorder (AUD) is negative affect during withdrawal, which often contributes to relapse and is thought to be caused by altered brain function, especially in circuits that are important mediators of emotional behaviors. Both the agranular insular cortex (AIC) and the basolateral amygdala (BLA) regulate emotions and are sensitive to ethanol-induced changes in synaptic plasticity. The AIC and BLA are reciprocally connected, however, and the effects of chronic ethanol exposure on this circuit have yet to be explored. Here, we use a combination of optogenetics and electrophysiology to examine the pre- and postsynaptic changes that occur to AIC – BLA synapses following withdrawal from 7- or 10-days of chronic intermittent ethanol (CIE) exposure. While CIE/withdrawal did not alter presynaptic glutamate release probably from AIC inputs, withdrawal from 10, but not 7, days of CIE increased AMPA receptor-mediated postsynaptic function at these synapses. Additionally, NMDA receptor-mediated currents evoked by electrical stimulation of the external capsule, which contains AIC afferents, were also increased during withdrawal. Notably, a single subanesthetic dose of ketamine administered at the onset of withdrawal prevented the withdrawal-induced increases in both AMPAR and NMDAR postsynaptic function. Ketamine also prevented the withdrawal-induced increases in anxiety-like behavior measured using the elevated zero maze. Together, these findings suggest that chronic ethanol exposure increases postsynaptic function within the AIC – BLA circuit and that ketamine can prevent ethanol withdrawal-induced alterations in synaptic plasticity and negative affect.

scholarly journals Chronic Ethanol and Withdrawal Differentially Modulate Pre- and Postsynaptic Function at Glutamatergic Synapses in Rat Basolateral Amygdala

2007 ◽  
Vol 98 (6) ◽  
pp. 3185-3196 ◽  
Author(s):  
Anna K. Läck ◽  
Marvin R. Diaz ◽  
Ann Chappell ◽  
Dustin W. DuBois ◽  
Brian A. McCool
Keyword(s):  
Ampa Receptor ◽  
Basolateral Amygdala ◽  
Physical Symptoms ◽  
Ethanol Exposure ◽  
Chronic Ethanol ◽  
Glutamatergic Synapses ◽  
Chronic Intermittent Ethanol ◽  
Acute Ethanol ◽  
Learned Fear ◽  
Fear And Anxiety

Withdrawal anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is long-lasting, can manifest well after the overt physical symptoms of withdrawal, and is frequently associated with relapse in recovering alcoholics. The neurobiological mechanisms governing these withdrawal-associated increases in anxiety are currently unknown. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates the expression of both learned fear and anxiety. Neurotransmitter system alterations within this brain region may therefore contribute to withdrawal-associated anxiety. Because evidence suggests that glutamate-gated neurotransmitter receptors are sensitive to acute ethanol exposure, we examined the effect of chronic intermittent ethanol (CIE) and withdrawal (WD) on glutamatergic synaptic transmission in the BLA. We found that slices prepared from CIE and WD animals had significantly increased contributions by synaptic NMDA receptors. In addition, CIE increased the amplitude of AMPA-receptor–mediated spontaneous excitatory postsynaptic currents (sEPSCs), whereas only WD altered the amplitude and kinetics of tetrodotoxin-resistant spontaneous events (mEPSCs). Similarly, the frequency of sEPSCs was increased in both CIE and WD neurons, although only WD increased the frequency of mEPSCs. These data suggest that CIE and WD differentially alter both pre- and postsynaptic properties of BLA glutamatergic synapses. Finally, we show that microinjection of the AMPA-receptor antagonist, DNQX, can attenuate withdrawal-related anxiety-like behavior. Together, our results suggest that increased glutamatergic function may contribute to anxiety expressed during withdrawal from chronic ethanol.

scholarly journals Moderate adolescent chronic intermittent ethanol exposure sex-dependently disrupts synaptic transmission and kappa opioid receptor function in the basolateral amygdala of adult rats

2020 ◽  
Author(s):  
Kathryn R. Przybysz ◽  
Meredith E. Gamble ◽  
Marvin R. Diaz
Keyword(s):  
Opioid Receptor ◽  
Basolateral Amygdala ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Adolescent Alcohol ◽  
Chronic Intermittent Ethanol ◽  
Glutamate Transmission

AbstractAdolescent alcohol exposure is associated with many negative outcomes that persist into adulthood, including altered affective and reward-related behaviors. However, the long-term neurological disruptions underlying these behavioral states are not fully understood. The basolateral amygdala (BLA) plays a critical role in many of these behaviors, and shifts in the excitatory/inhibitory balance in this area are capable of directly modulating their expression. While changes to BLA physiology have been demonstrated during the acute withdrawal phase following adolescent ethanol exposure, no studies to date have examined whether these persist long-term. The kappa opioid receptor (KOR) system is a neuromodulatory system that acts as a prominent mediator of negative affective behaviors, and alterations of this system have been implicated in the behavioral profile caused by chronic alcohol exposure in adulthood. Notably, in the BLA, the KOR system undergoes functional changes between adolescence and adulthood, but whether BLA KORs are functionally disrupted by adolescent ethanol exposure has not been examined. In this study, we exposed male and female Sprague-Dawley rats to a vapor inhalation model of moderate adolescent chronic intermittent ethanol (aCIE) and examined the long-term effects on GABAergic and glutamatergic neurotransmission within the adult BLA using whole-cell patch-clamp electrophysiology. We also assessed how KOR activation modulated these neurotransmitter systems in aCIE versus control rats using the selective KOR agonist, U69593. This investigation revealed that aCIE exposure disrupted basal glutamate transmission in females by increasing spontaneous excitatory postsynaptic current (sEPSC) frequency, while having no effects on glutamate transmission in males or GABA transmission in either sex. Interestingly, we also found that aCIE exposure unmasked a KOR-mediated suppression of spontaneous inhibitory postsynaptic current (sIPSC) frequency and sEPSC amplitude only in males, with no effects of aCIE exposure on KOR function in females. Together, these data suggest that moderate-level adolescent ethanol exposure produces long-term changes to BLA physiology and BLA KOR function, and that these changes are sex-dependent. This is the first study to examine persistent adaptations to both BLA physiology and KOR function following adolescent alcohol exposure, and opens a broad avenue for future investigation into other neurobiological and behavioral consequences of adolescent ethanol exposure-induced disruptions of these systems.

scholarly journals Heterogeneous Firing Responses Predict Diverse Couplings to Presynaptic Activity in mice Layer V Pyramidal Neurons

2016 ◽  
Author(s):  
Yann Zerlaut ◽  
Alain Destexhe
Keyword(s):  
Membrane Potential ◽  
Synaptic Input ◽  
Pyramidal Neurons ◽  
Network Activity ◽  
Local Network ◽  
Potential Fluctuations ◽  
Branching Rule ◽  
Layer V ◽  
Different Levels ◽  
Membrane Potential Fluctuations

In this study, we present a theoretical framework combining experimental characterizations and analytical calculus to capture the firing rate input-output properties of single neurons in the fluctuation-driven regime. Our framework consists of a two-step procedure to treat independently how the dendritic input translates into somatic fluctuation variables, and how the latter determine action potential firing. We use this framework to investigate the functional impact of the heterogeneity in firing responses found experimentally in young mice layer V pyramidal cells. We first design and calibrate in vitro a simplified morphological model of layer V pyramidal neurons with a dendritic tree following Rall's branching rule. Then, we propose an analytical derivation for the membrane potential fluctuations at the soma as a function of the properties of the synaptic input in dendrites. This mathematical description allows us to easily emulate various forms of synaptic input: either balanced, unbalanced, synchronized, purely proximal or purely distal synaptic activity. We find that those different forms of input activity lead to various impact on the membrane potential fluctuations properties, thus raising the possibility that individual neurons will differentially couple to specific forms of activity as a result of their different firing response. We indeed found such a heterogeneous coupling between synaptic input and firing response for all types of presynaptic activity. This heterogeneity can be explained by different levels of cellular excitability in the case of the balanced, unbalanced, synchronized and purely distal activity. A notable exception appears for proximal dendritic inputs: increasing the input level can either promote firing response in some cells, or suppress it in some other cells whatever their individual excitability. This behavior can be explained by different sensitivities to the speed of the fluctuations, which was previously associated to different levels of sodium channel inactivation and density. Because local network connectivity rather targets proximal dendrites, our results suggest that this aspect of biophysical heterogeneity might be relevant to neocortical processing by controlling how individual neurons couple to local network activity.

scholarly journals Synaptic GABAA Activation Inhibits AMPA-Kainate Receptor–Mediated Bursting in the Newborn (P0–P2) Rat Hippocampus

2000 ◽  
Vol 83 (1) ◽  
pp. 359-366 ◽  
Author(s):  
Karri Lamsa ◽  
J. Matias Palva ◽  
Eva Ruusuvuori ◽  
Kai Kaila ◽  
Tomi Taira
Keyword(s):  
Pyramidal Neurons ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Neuronal Population ◽  
Excitatory Input ◽  
Calcium Oscillations ◽  
Rat Hippocampus ◽  
Network Activity ◽  
Ca1 Pyramidal Cells

The mechanisms of synaptic transmission in the rat hippocampus at birth are assumed to be fundamentally different from those found in the adult. It has been reported that in the CA3-CA1 pyramidal cells a conversion of “silent” glutamatergic synapses to conductive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synapses starts gradually after P2. Further, GABA via its depolarizing action seems to give rise to grossly synchronous yet slow calcium oscillations. Therefore, GABA is generally thought to have a purely excitatory rather than an inhibitory role during the first postnatal week. In the present study field potential recordings and gramicidin perforated and whole cell clamp techniques as well as K+-selective microelectrodes were used to examine the relative contributions of AMPA and GABAA receptors to network activity of CA3-CA1 pyramidal cells in the newborn rat hippocampus. As early as postnatal day( P 0–P2), highly coherent spontaneous firing of CA3 pyramidal cells was seen in vitro. Negative-going extracellular spikes confined to periodic bursts (interval 16 ± 3 s) consisting of 2.9 ± 0.1 spikes were observed in stratum pyramidale. The spikes were accompanied by AMPA-R–mediated postsynaptic currents (PSCs) in simultaneously recorded pyramidal neurons (7.6 ± 3.0 unitary currents per burst). In CA1 pyramidal cells synchronous discharging of CA3 circuitry produced a barrage of AMPA currents at >20 Hz frequencies, thus demonstrating a transfer of the fast CA3 network activity to CA1 area. Despite its depolarizing action, GABAA-R–mediated transmission appeared to exert inhibition in the CA3 pyramidal cell population. The GABAA-R antagonist bicuculline hypersynchronized the output of glutamatergic CA3 circuitry and increased the network-driven excitatory input to the pyramidal neurons, whereas the GABAA-R agonist muscimol (100 nM) did the opposite. However, the occurrence of unitary GABAA-R currents was increased after muscimol application from 0.66 ± 0.16 s−1 to 1.43 ± 0.29 s−1. It was concluded that AMPA synapses are critical in the generation of spontaneous high-frequency bursts in CA3 as well as in CA3-CA1 transmission as early as P0–P2 in rat hippocampus. Concurrently, although GABAA-R–mediated depolarization may excite hippocampal interneurons, in CA3 pyramidal neurons it can restrain excitatory inputs and limit the size of the activated neuronal population.

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