Biology subjects

Wiltgen, B. J.

Publications and source records attributed to Wiltgen, B. J..

4 recordsLinked to original sources

bioRxiv2022

Phasic locus coeruleus activity facilitates hippocampus-dependent trace fear memory formation

Locus coeruleus (LC) projections to the hippocampus play a critical role in learning and memory. However, the precise timing of LC-hippocampus communication during learning and which LC-derived neurotransmitters are important for memory formation in the hippocampus are currently unknown. Although the LC is typically thought to modulate neural activity via the release of norepinephrine, several recent studies have suggested that it may also release dopamine into the hippocampus and other cortical regions. In some cases, it appears that dopamine release from LC into the hippocampus may be more important for memory than norepinephrine. Here, we extend these data by characterizing the phasic responses of the LC and its projections to the dorsal hippocampus during trace fear conditioning. We find that the LC and its projections to the hippocampus respond to task-relevant stimuli and that amplifying these responses with optogenetic stimulation can enhance long-term memory formation. We also demonstrate that LC activity increases both norepinephrine and dopamine content in the dorsal hippocampus and that the timing of hippocampal dopamine release during trace fear conditioning is similar to the timing of LC activity. Finally, we show that hippocampal dopamine is important for trace fear memory formation, while norepinephrine is not.

animal behavior and cognition↗

bioRxiv2022

Encoding object-location memories along the proximodistal axis of CA1

The hippocampus is thought to combine "what" and "where" information from the cortex so that objects and events can be represented within the spatial context in which they occur. Surprisingly then, these distinct types of information remain partially segregated in the output region of the hippocampus, area CA1. In this region, objects preferentially activate neurons in the distal segment (adjacent to the subiculum) while spatial locations are precisely represented by neurons in the proximal segment (adjacent to CA2). This difference likely results from distinct anatomical connections; proximal CA1 receives direct input from the medial entorhinal cortex (which encodes spatial context) whereas distal CA1 has reciprocal connections with the lateral entorhinal cortex (which encodes objects and events). Based on these findings, it has been proposed that CA1 contains two distinct representations; one that encodes the animals spatial location and another that encodes objects that are present in the environment. The current study aimed to determine the role of distal CA1 in learning the location of objects in an environment. To do this, we first examined c-Fos expression in proximal and distal CA1 to see if we could replicate previous findings and confirm that neurons in these distinct segment are responsive to different stimuli. As previous studies indicate that catecholamines can regulate the activity of segments of CA1, we then investigate the role of catecholamines on learning object locations using 6-OHDA or SCH23390 to lesion catecholaminergic input and block D1/D5 receptors, respectively. Finally, we monitored calcium activity with fiber photometry while animals performed a hippocampal-dependent object location memory task.

animal behavior and cognition↗

bioRxiv2022

The hippocampus contributes to retroactive stimulus associations in trace fear conditioning

Binding events that occur at different times is essential for memory formation. In trace fear conditioning, animals associate a tone and footshock despite no temporal overlap. The hippocampus is thought to mediate this learning by maintaining a memory of the tone until shock occurrence, however evidence for sustained hippocampal tone representations is lacking. Here we demonstrate a retrospective role for the hippocampus in trace fear conditioning. Bulk calcium imaging revealed sustained increases in CA1 activity after footshock that were not observed after tone termination. Optogenetic silencing of CA1 immediately after footshock impaired subsequent memory. Additionally, footshock increased the number of sharp wave-ripples compared to baseline during conditioning. Therefore, post-shock hippocampal activity likely supports learning by reactivating and linking latent tone and shock representations. These findings highlight an underappreciated function of post-trial hippocampal activity in enabling retroactive temporal associations during new learning, as opposed to persistent maintenance of stimulus representations.

animal behavior and cognition↗

bioRxiv2019

Recently formed context fear memories can be retrieved without the hippocampus

The current study determined if inactivation of the dorsal hippocampus impairs the retrieval of newly formed context fear memories. This region was silencing by activating inhibitory neurons or by hyperpolarizing pyramidal cells directly. When inhibitory neurons were stimulated with ChR2, memory retrieval was significantly impaired. In contrast, when the same neurons were activated with the excitatory DREADD hM3Dq, retrieval was not affected. This dissociation was not due to differences in inhibition, as both manipulations activated interneurons and reduced excitation throughout the dorsal hippocampus. Therefore, we hypothesize that the retrieval deficit caused by ChR2 stimulation is due to an immediate reduction in hippocampal activity that does not provide enough time for other brain regions to compensate. Stimulation of DREADDs, on the other hand, produces a gradual loss of excitation that takes several minutes to reach asymptote. This appears to be a sufficient amount of time for extra-hippocampal structures to become engaged and express context fear. Implications for theories of hippocampal function, systems consolidation and memory retrieval are discussed.

neuroscience↗