Biology subjects

Ramanathan, K. R.

Publications and source records attributed to Ramanathan, K. R..

3 recordsLinked to original sources

bioRxiv2021

Ventral hippocampus mediates the context-dependence of two-way signaled avoidance in male rats

Considerable work indicates that instrumental responding is context-dependent, but the neural mechanisms underlying this phenomenon are poorly understood. Given the important role for the hippocampal formation in contextual processing, we hypothesized that reversible inactivation of the hippocampus would impair the context-dependence of active avoidance. To test this hypothesis, we used a two-way signaled active avoidance (SAA) task that requires rats to shuttle across a divided chamber during a tone CS in order to avoid a footshock US. After training, avoidance responding was assessed in an extinction test in both the training context and a novel context in a counterbalanced order. Rats performed significantly more avoidance responses in the training context than in the novel context, demonstrating the context-dependence of shuttle avoidance behavior. To examine the role of the hippocampus in the context-dependence of SAA, we reversibly inactivated either the dorsal (DH) or ventral hippocampus (VH) prior to testing. Inactivation of the VH eliminated the context-dependence of SAA and elevated avoidance responding in the novel context to levels similar to that expressed in the training context. In contrast, DH inactivation had no effect on avoidance in either context, and neither manipulation affected freezing behavior. Therefore, the integrity of the VH, but not DH, is required for the expression context-dependence of avoidance behavior.

neuroscience↗

bioRxiv2021

Behavioral and brain mechanisms mediating conditioned flight behavior in rats

Environmental contexts and associative learning can inform animals of potential threats, though it is currently unknown how contexts bias defensive transitions. Here we investigated context-dependent flight responses in the Pavlovian serial-compound stimulus (SCS) paradigm. We show here that SCS-evoked flight behavior in male and female rats is dependent on contextual fear. Flight was reduced in the conditioning context after context extinction and could be evoked in a different shock-associated context. Although flight was exclusive to white noise stimuli, it was nonetheless associative insofar as rats that received an equal number of unpaired USs did not show flight-like behavior. Finally, we found that inactivation of either the central nucleus of the amygdala (CeA) or bed nucleus of the stria terminalis (BNST) attenuated both contextual fear and flight responses. This work demonstrates that contextual fear summates with cued and innate fear to drive a high fear state and freeze-to-flight transitions.

neuroscience↗

bioRxiv2018

Nucleus reuniens is required for encoding and retrieving precise contextual fear memories in rats

The nucleus reuniens (RE) is a ventral midline thalamic nucleus that interconnects the medial prefrontal cortex (mPFC) and hippocampus (HPC). Considerable data indicate that HPC-mPFC circuits are involved in contextual and spatial memory; however, it is not clear whether the RE mediates the acquisition or retrieval of these memories. To examine this question, we inactivated the RE with muscimol before either the acquisition or retrieval of Pavlovian fear conditioning in rats; freezing served as the index of fear. We found that RE inactivation before conditioning impaired the acquisition of contextual freezing, whereas inactivation of the RE prior to retrieval testing increased the generalization of freezing to a novel context; inactivation of the RE did not affect either the acquisition or expression of auditory fear conditioning. Interestingly, contextual conditioning impairments were absent when retrieval testing was also conducted after RE inactivation. Contextual memories acquired under RE inactivation were hippocampal-independent, insofar as contextual freezing in rats conditioned under RE inactivation was insensitive to intra-hippocampal infusions of the NMDA receptor antagonist, D,L-amino-5-phosophonovaleric acid (APV). Together, these data reveal that the RE supports hippocampal-dependent encoding of precise contextual memories that allow discrimination of dangerous from safe contexts. When the RE is inactive, however, alternate neural systems acquire an impoverished contextual memory that is only expressed when the RE is offline.\n\nSIGNIFICANCE STATEMENTThe midline thalamic nucleus reuniens (RE) coordinates communication between the hippocampus and medial prefrontal cortex, brain areas critical for contextual and spatial memory. Here we show that temporary pharmacological inactivation of RE impairs the acquisition and precision of contextual fear memories after Pavlovian fear conditioning in rats. However, inactivating the RE prior to retrieval testing restored contextual memory in rats conditioned after RE inactivation. Critically, we show that imprecise contextual memories acquired under RE inactivation are learned independently of the hippocampus. These data reveal that the RE is required for hippocampal-dependent encoding of precise contextual memories to support the discrimination of safe and dangerous contexts.

neuroscience↗