Prefrontal Cortex Drives Distinct Projection Neurons in the Basolateral Amygdala

McGarry, Laura M.; Carter, Adam G.

doi:10.1016/j.celrep.2017.10.046

Cited by 121 publications

(99 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The addition of 4-AP and subsequent blockade of voltage-gated potassium channels induced additional depolarization at the terminals so that ChR2-mediated depolarization was then enough to trigger glutamate release (Figure 1). Our results are consistent with the monosynaptic nature of the mPFC -BLA projections that has demonstrated previously by others (Arruda-Carvalho and Clem, 2014;Cho et al, 2013;Kiritoshi and Neugebauer, 2018;Little and Carter, 2013;McGarry and Carter, 2017). Importantly, we compared paired-pulse ratios recorded in the presence of TTX and 4-AP as well as under standard conditions and we did not observe a significant difference, suggesting that our recordings did not contain significant polysynaptic contributions to our glutamatergic recordings.…”

Section: Discussionsupporting

confidence: 92%

“…withdrawal from chronic ethanol exposure may cause the IL/vmPFC terminals to engage with a different population of neurons or the amount of stimulation we had to apply to these terminals to elicit comparable EPSCs in the AIR and CIE/WD animals may have been different, resulting in greater stimulation and GABAergic release in our withdrawal recordings. The latter hypothesis is feasible considering the fact that the prefrontal cortex has been shown the drive distinct populations of projection neurons in the BLA (Laura McGarry et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…A leading neurobiological model of emotional regulation, supported by both animal and human data, is that the prefrontal cortex mediates the expression of negative affect through powerful top-down control of the amygdala (Phelps and LeDoux, 2005). Specifically, the dorsal and ventral subdivisions of the medial prefrontal cortex (mPFC) have strong reciprocal connectivity with neurons in the BLA (Little and Carter, 2013;McGarry and Carter, 2017) and have been implicated in controlling a variety of emotional-related behaviors (Arruda-Carvalho and Clem, 2015;Sotres-Bayon and Quirk, 2010). Interestingly, these different subregions and their projections to the BLA play dichotomous roles in fear learning and extinction.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons

McGinnis

Parrish

Chappell

et al. 2019

Preprint

View full text Add to dashboard Cite

The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) have strong reciprocal connectivity. Projections from the BLA to the mPFC can bidirectionally modulate anxiety-related behaviors but it is unclear if the same is true for mPFC to BLA projections. Our laboratory is specifically interested in withdrawal-related anxiety-like behavior and the underlying synaptic plasticity. Here, we use optogenetics and chemogenetics to characterize the neurophysiological and behavioral alterations produced by chronic ethanol exposure and withdrawal on dorsal mPFC/prelimbic (dmPFC/PL) and ventral mPFC (vmPFC/IL) terminals in the BLA. We exposed adult male Sprague-Dawley rats to chronic intermittent ethanol (CIE) using vapor chambers, measured anxiety-like behavior on the elevated zero maze (EZM), and used electrophysiology to record glutamatergic and GABAergic responses in BLA principal neurons. We found that 24-hour withdrawal following a 7-day CIE exposure significantly increased the glutamate release probability from PL/dmPFC terminals, but significantly decreases the glutamate release probability from IL/vmPFC terminals. Chemogenetic inhibition of PL/dmPFC terminals in the BLA attenuated the increased withdrawal-dependent, anxiety-like behavior. These data demonstrate that chronic ethanol exposure and withdrawal strengthens the PL/dmPFC -BLA pathway but weakens the IL/vmPFC -BLA pathway. Moreover, we provide novel evidence that the PL/dmPFC -BLA pathway can modulate anxiety-like behavior. These findings suggest that mPFC-BLA circuits known to regulate the acquisition of aversive behaviors are up-regulated by chronic ethanol while those involved with the extinction of these behaviors are down-regulated. Significance StatementAccumulating evidence suggests that the medial prefrontal cortex and its projections to the basolateral amygdala bidirectionally modulate fear-related behaviors. Since the neuronal circuits for fear and anxiety are thought to overlap, we sought to examine the role of prelimbic and infralimbic subdivisions of the medial prefrontal cortex and their inputs to the basolateral amygdala in regulating anxiety. Specifically, we focused on alcohol withdrawal-induced anxietylike behavior, which is a commonly reported cause of relapse in human alcoholics. In our study, we used optogenetics and chemogenetics to demonstrate, for the first time, that withdrawal from chronic ethanol exposure strengthens prelimbic synapses, but weakens infralimbic synapses in the basolateral amygdala and that inhibiting glutamate release from prelimbic terminal in the basolateral amygdala reduces anxiety-like behavior.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons

McGinnis

Parrish

Chappell

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Next, we measured light-evoked input-specific quantal EPSCs (qoEPSCs) by replacing our intracellular medium’s calcium with strontium to desynchronize transmitter release (Figure 5) (Britt et al, 2012; McGarry and Carter, 2017). qoEPSCs amplitude provide a direct estimate of postsynaptic efficacy measure and qoEPSC frequency was taken as an indirect indication of the number of connections (Goda and Stevens, 1994).…”

Section: Resultsmentioning

confidence: 99%

Cell-type and endocannabinoid specific synapse connectivity in the adult nucleus accumbens core

Deroche

Lassalle

Manzoni

2019

Preprint

View full text Add to dashboard Cite

The nucleus accumbens (NAc) is a mesocorticolimbic structure that integrates cognitive, emotional and motor functions. Although its role in psychiatric disorders is widely acknowledged, the understanding of its circuitry is not complete. Here we combined optogenetic and whole-cell recordings to draw a functional portrait of excitatory disambiguated synapses onto D1 and D2 medium spiny neurons (MSNs) in the adult mouse NAc core. Comparing synaptic properties of ventral hippocampus (vHipp), basolateral amygdala (BLA) and prefrontal cortex (PFC) inputs revealed a hierarchy of synaptic inputs and feedforward inhibition that depends on the identity of the postsynaptic target MSN. Thus, the BLA is the dominant excitatory pathway onto D1 MSNs (BLA > PFC = vHipp) while PFC inputs dominate D2 MSNs (PFC > vHipp > BLA). Feedforward inhibition of MSN firing too, was input and cell-type specific: while minimal at vHipp-D1 and vHipp-D2 inputs; it inhibited with similar efficacy BLA-D1 or BLA-D2 inputs, was minimal at PFC-D1 but maximal at PFC-D2 inputs. We also tested the hypothesis that endocannabinoids endow excitatory circuits with pathway- and cell-specific plasticity. Thus, while CB1 receptors (CB1R) uniformly depress excitatory pathways irrespective of MSNs identity, TRPV1 receptors (TRPV1R) bidirectionally control inputs onto the NAc core in a pathway-specific manner. Finally, we show how the interplay of TRPV1R/CB1R shapes plasticity at identified BLA-NAc synapses. Together these data shed new light on synapse and circuit specificity in the adult NAc core and illustrate how endocannabinoids contribute to pathway-specific synaptic plasticity.SIGNIFICANCE STATEMENTWe examined the impact of connections from the ventral hippocampus (vHipp,) basolateral amygdala (BLA) and prefrontal cortex (PFC) onto identified medium spiny neurons (MSN) in the adult accumbens core. We found BLA inputs were strongest at D1 MSNs while PFC inputs dominate D2 MSNs. We evaluated the role of the endocannabinoid system in pathway- and cell-specific plasticity and found that CB1 receptors (CB1R) and TRPV1 receptors (TRPV1R) bidirectionally control synaptic transmission and plasticity onto accumbens’ MSNs in a pathway- and cell-specific manner. Finally, we clarify how the interplay of TRPV1R/CB1R shapes plasticity at identified BLA-NAc synapses.

show abstract

“…Recent studies have demonstrated segregation of projection defined cell types in the mouse BLA 20,21 . Genetically distinct BLA cell populations with unique functional and connectional phenotypes also have been identified 22 .…”

Section: Introductionmentioning

confidence: 99%

Connectivity characterization of the mouse basolateral amygdalar complex

Hintiryan

Bowman

Johnson

et al. 2019

Preprint

View full text Add to dashboard Cite

The basolateral amygdalar complex (BLA) is implicated in behavioral processing ranging from fear acquisition to addiction. Newer methods like optogenetics have enabled the association of circuitspecific functionality to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. In this work, we applied computational analysis techniques to the results of our circuittracing experiments to create a foundational, comprehensive, multiscale connectivity atlas of the mouse BLA. The analyses identified three domains within the classically defined anterior BLA (BLAa) that house target-specific projection neurons with distinguishable cell body and dendritic morphologies. Further, we identify brain-wide targets of projection neurons located in the three BLAa domains as well as in the posterior BLA (BLAp), ventral BLA (BLAv), lateral (LA), and posterior basomedial (BMAp) nuclei. Projection neurons that provide input to each nucleus are also identifed. Functional characterization of some projection-defined BLA neurons were demonstrated via optogenetic and recording experiments. Hypotheses relating function to connection-defined BLA cell types are proposed. rACAd, Anterior cingulate cortical area, dorsal part, rostral region cACAd, Anterior cingulate cortical area, dorsal part, caudal region ACAv, Anterior cingulate cortical area, ventral part rACAv, Anterior cingulate cortical area, ventral part, rostral region cACAv, Anterior cingulate cortical area, ventral part, caudal region ACB, Nucleus accumbens AD, Anterodorsal nucleus of the thalamus ADP, Anterodorsal preoptic nucleus of the hypothalamus AHN, Anterior hypothalamic nucleus AI, Agranular insular cortical area AId, Agranular insular cortical area, dorsal part AIv, Agranular insular cortical area, ventral part AIv, Agranular insular cortical area, posterior part AM, Anteromedial nucleus of the thalamus AMd, Anteromedial nucleus of the thalamus, dorsal part AMv, Anteromedial nucleus of the thalamus, ventral part AON, Anterior olfactory nucleus AONm, Anterior olfactory nucleus, medial part AONpv, Anterior olfactory nucleus, posteroventral part ARH, Arcuate hypothalamic nucleus AUD, Auditory cortical area AUDd, Dorsal auditory cortical area AUDp, Primary auditory cortical area AUDv, Ventral auditory cortical area AV, Anteroventral nucleus of the thalamus AVP, Anteroventral preoptic nucleus AVPV, Anteroventral periventricular nucleus bic, Brachium of the inferior colliculus BLA, Basolateral amygdalar complex BLAa, Basolateral amygdalar nucleus, anterior part BLA.am, Basolateral amydalar nucleus, anterior part, medial domain BLA.al, Basolateral amydalar nucleus, anterior part, lateral domain BLA.ac, Basolateral amydalar nucleus, anterior part, caudal domain BLAp, Basolateral amygdalar nucleus, posterior part BLAv, Basolateral amygdalar nucleus, ventral part BMA, Basomedial amygdalar nucleus BMAa, Basomedial amygdalar nucleus, anterior part BMAp, Basomedial...

show abstract

Prefrontal Cortex Drives Distinct Projection Neurons in the Basolateral Amygdala

Cited by 121 publications

References 45 publications

Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons

Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons

Cell-type and endocannabinoid specific synapse connectivity in the adult nucleus accumbens core

Connectivity characterization of the mouse basolateral amygdalar complex

Contact Info

Product

Resources

About