Enhanced excitability in the infralimbic cortex produces anxiety-like behaviors

Abstract The onset of several neuropsychiatric disorders including anxiety disorders coincides with adolescence. Consistently, threat extinction, which plays a key role in the regulation of anxiety-related behaviors, is diminished during adolescence. Furthermore, this attenuated threat extinction during adolescence is associated with an altered synaptic plasticity in the infralimbic medial prefrontal cortex (IL-mPFC), a brain region critical for threat extinction. However, the mechanism underlying the altered plasticity in the IL-mPFC during adolescence is unclear. Given the purported role of vasoactive intestinal polypeptide expressing interneurons (VIPINs) in disinhibition and hence their potential to affect cortical plasticity, we examined whether VIPINs exhibit an adolescence-specific plasticity in the IL-mPFC. We observed an increase in GABAergic transmission and a decrease in excitability in VIPINs during adolescence. Male mice show a significantly higher VIPIN-pyramidal neuron GABAergic transmission compared with female mice. The observed increase in GABAergic transmission and a decrease in membrane excitability in VIPINs during adolescence could play a role in the altered plasticity in the adolescent IL-mPFC. Furthermore, the suppression of VIPIN-mediated GABAergic transmission in females might be relevant to sex differences in anxiety disorders.

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2418 Projection sites of infralimbic cortex (area 25) of the monkey

Neuroscience Research ◽

10.1016/s0168-0102(97)90776-8 ◽

1997 ◽

Vol 28 ◽

pp. S281 ◽

Cited By ~ 1

Author(s):

Tanemichi Chiba ◽

Katsuma Nakano

Keyword(s):

Infralimbic Cortex ◽

Cortex Area

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Ketamine triggers rapid antidepressant effects by modulating synaptic plasticity in a new depressive-like mouse model based on astrocyte glutamate transporter GLT-1 knockdown in infralimbic cortex

Revista de Psiquiatría y Salud Mental ◽

10.1016/j.rpsm.2021.09.002 ◽

2021 ◽

Author(s):

M. Neus Fullana ◽

Verónica Paz ◽

Francesc Artigas ◽

Analia Bortolozzi

Keyword(s):

Synaptic Plasticity ◽

Mouse Model ◽

Glutamate Transporter ◽

Infralimbic Cortex ◽

Model Based ◽

Antidepressant Effects

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Dissociation of Appetitive Overexpectation and Extinction in the Infralimbic Cortex

Cerebral Cortex ◽

10.1093/cercor/bhy248 ◽

2018 ◽

Vol 29 (9) ◽

pp. 3687-3701 ◽

Cited By ~ 2

Author(s):

Belinda P P Lay ◽

Melissa Nicolosi ◽

Alexandra A Usypchuk ◽

Guillem R Esber ◽

Mihaela D Iordanova

Keyword(s):

Behavioral Change ◽

Reward Learning ◽

Behavioral Modification ◽

Test Drug ◽

Infralimbic Cortex ◽

Stimulus Response ◽

Conditioned Responses ◽

Conditioned Responding ◽

Drug Free

Abstract Behavioral change is paramount to adaptive behavior. Two ways to achieve alterations in previously established behavior are extinction and overexpectation. The infralimbic (IL) portion of the medial prefrontal cortex controls the inhibition of previously established aversive behavioral responses in extinction. The role of the IL cortex in behavioral modification in appetitive Pavlovian associations remains poorly understood. Here, we seek to determine if the IL cortex modulates overexpectation and extinction of reward learning. Using overexpectation or extinction to achieve a reduction in behavior, the present findings uncover a dissociable role for the IL cortex in these paradigms. Pharmacologically inactivating the IL cortex left overexpectation intact. In contrast, pre-training manipulations in the IL cortex prior to extinction facilitated the reduction in conditioned responding but led to a disrupted extinction retrieval on test drug-free. Additional studies confirmed that this effect is restricted to the IL and not dependent on the dorsally-located prelimbic cortex. Together, these results show that the IL cortex underlies extinction but not overexpectation-driven reduction in behavior, which may be due to regulating the expression of conditioned responses influenced by stimulus–response associations rather than stimulus–stimulus associations.

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Interaction between perineuronal nets and ketamine in antidepressant action

10.1101/2021.05.30.446326 ◽

2021 ◽

Author(s):

Calvin K Young ◽

Kachina G Kinley ◽

Neil McNaughton

Keyword(s):

Suicide Risk ◽

Forced Swim Test ◽

Perineuronal Nets ◽

Scaffolding Proteins ◽

Infralimbic Cortex ◽

Swim Test ◽

Forced Swim ◽

Antidepressant Effects ◽

Immobility Time ◽

Antidepressant Action

Depression is highly prevalent, increases suicide risk, and is now the leading cause of disability worldwide. Our ability to treat depression is hampered by the lack of understanding of its biological underpinnings and of the mode of action of effective treatments. We hypothesised that the scaffolding proteins in the medial frontal cortex play a major role in effective antidepressant action. We implanted cannulae into the infralimbic cortex to inject chABC and locally remove perineuronal nets and then tested for antidepressant effects with the forced swim test. We further tested if systemic injections of ketamine had an additive effect. Our preliminary data indicate that neither the removal of these scaffolding proteins nor ketamine were sufficient to decrease depression-like behaviour, but may interact synergistically to decrease immobility time in the forced swim test.

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