Biology subjects

Chandran, S. K.

Publications and source records attributed to Chandran, S. K..

4 recordsLinked to original sources

bioRxiv2024

Chemogenetic attenuation of PFC pyramidal neurons restores deficits in recognition memory following adolescent NMDA receptor blockade

During adolescence, the prefrontal cortex (PFC) undergoes dramatic developmental changes, including fine-tuning the balance between excitatory glutamate and inhibitory GABA transmission (i.e., the E/I balance). This process is critical for intact cognitive function and social behavior in adulthood, and its disruption is associated with several psychiatric disorders including schizophrenia (SZ). While acute NMDA receptor (NMDAr) blockade leads to excess glutamate transmission in the PFC, the long-term consequences of MK-801 administration during early adolescence on the E/I balance in adulthood have not been extensively studied. In the current study, we show that chronic MK-801 administration during early adolescence leads to abnormalities in recognition memory and social behavior as well as reduced frequency of miniature inhibitory post-synaptic currents (mIPSCs) in mPFC of adult male rats, with no change in excitatory currents or basal activity. We further show that chemogenetic attenuation of prelimbic mPFC pyramidal neurons reversed deficits in recognition memory, but not social behavior. These findings emphasize the critical role played by NMDAr during adolescence on the E/I balance as well as cognition and social function in adulthood. Moreover, these findings implicate the therapeutic outcomes of reduced mPFC pyramidal neuron activity in recognition memory deficits in early-adolescence MK-801-treated rats. Since recognition memory deficits are key components of the cognitive deficits in SZ, these findings suggest that the future development of treatments aimed at alleviating the cognitive deficits in SZ should focus on regulating the prefrontal E/I balance.

neuroscience↗

bioRxiv2022

Intrinsic excitability in layer IV-VI anterior insula to basolateral amygdala projection neurons encodes the confidence of taste valence

Avoiding potentially harmful, and consuming safe food is crucial for the survival of living organisms. However, sensory information can change its valence following conflicting experiences. Novelty and aversiveness are the two crucial parameters defining the currently perceived valence of taste. Importantly, the ability of a given taste to serve as CS in conditioned taste aversion (CTA) is dependent on its valence. Activity in anterior insula (aIC) layer IV-VI pyramidal neurons projecting to the basolateral amygdala (BLA) is correlative and necessary for CTA learning and retrieval, as well as the expression of neophobia towards novel tastants, but not learning taste familiarity. Yet, the cellular mechanisms underlying the updating of taste valence representation in this specific pathway are poorly understood. Here, using retrograde viral tracing and whole cell patch-clamp electrophysiology in trained mice, we demonstrate that the intrinsic properties of deep-lying layer IV-VI, but not superficial layer I-III aIC-BLA neurons, are differentially modulated by both novelty and valence, reflecting the subjective predictability of taste valence arising from prior experience. These correlative changes in the profile of intrinsic properties of LIV-VI aIC-BLA neurons were detectable following both simple taste experiences, as well as following memory retrieval, extinction learning and reinstatement.

neuroscience↗

bioRxiv2021

Insula to mPFC reciprocal connectivity differentially underlies novel taste neophobic response and learning

To survive in an ever-changing environment, animals must detect and learn salient information. The anterior insular cortex (aIC) and medial prefrontal cortex (mPFC) are heavily implicated in salience and novelty processing, and specifically, the processing of taste sensory information. Here, we examined the role of aIC-mPFC reciprocal connectivity in novel taste neophobia and memory formation, in mice. Using pERK and neuronal intrinsic properties as markers for neuronal activation, and retrograde AAV (rAAV) constructs for connectivity, we demonstrate a correlation between aIC-mPFC activity and novel taste experience. Furthermore, by expressing inhibitory chemogenetic receptors in these projections, we show that aIC-to-mPFC activity is necessary for both taste neophobia and its attenuation. However, activity within mPFC-to-aIC projections is essential only for the neophobic reaction but not for the learning process. These results provide an insight into the cortical circuitry needed to detect, react to- and learn salient stimuli, a process critically involved in psychiatric disorders.

neuroscience↗

bioRxiv2021

Parvalbumin Interneurons Inhibition onto BLA Projecting Neurons of the Anterior Insula Orchestrates Aversive Taste Memory Retrieval

Memory retrieval refers to the fundamental ability of organisms to make use of acquired, sometimes inconsistent, information about the world. While memory acquisition has been studied extensively, the neurobiological mechanisms underlying memory retrieval remain largely unknown. The anterior insula (aIC) is indispensable in the ability of mammals to retrieve associative information regarding tastants that have been previously linked with gastric malaise. Here, we show that aversive taste memory retrieval promotes cell-type-specific activation in the aIC. Aversive, but not appetitive taste memory retrieval, relies on specific changes in activity and connectivity at parvalbumin (PV) inhibitory synapses onto aIC pyramidal neurons projecting to the basolateral amygdala. PV aIC interneurons, coordinate aversive taste memory retrieval, and are necessary for its dominance when conflicting internal representations are encountered. This newly described interaction of PV and a subset of excitatory neurons can explain the coherency of aversive memory retrieval, an evolutionary pre-requisite for animal survival. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/433377v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1e73ba2org.highwire.dtl.DTLVardef@1fc234dorg.highwire.dtl.DTLVardef@719d74org.highwire.dtl.DTLVardef@1184bb9_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIRetrieval of Conditioned Taste Aversion (CTA) memories at the anterior insular cortex activates Parvalbumin (PV) interneurons and increases synaptic inhibition onto activated pyramidal neurons projecting to the basolateral amygdala (aIC-BLA). C_LIO_LIUnlike innately appetitive taste memory retrieval, CTA retrieval increases the amplitude and frequency of synaptic inhibition onto aIC-BLA projecting neurons, that is dependent on activity in aIC PV interneurons. C_LIO_LIActivation of aIC PV interneurons is necessary for the expression of learned taste avoidance, in both sexes, regardless of stimulus identity. C_LIO_LIExtinction of aversive taste memories suppresses the frequency, but not the amplitude of synaptic inhibition on aIC-BLA projecting neurons. C_LIO_LIThe reinstatement of aversive taste memories following extinction is dependent upon activation of aIC PV interneurons and increases in the frequency of inhibition on aIC-BLA projecting neurons. C_LI

neuroscience↗