Interaction between hippocampal-prefrontal plasticity and thalamic-prefrontal activity

Abstract

The prefrontal cortex integrates a variety of cognition-related inputs, either unidirectional, e.g., from the hippocampal formation, or bidirectional, e.g., with the limbic thalamus. While the former is usually implicated in synaptic plasticity, the latter is better known for regulating ongoing activity. Interactions between these processes via prefrontal neurons are possibly important for linking mnemonic and executive functions. Our work further elucidates such dynamics using in vivo electrophysiology in rats. First, we report that electrical pulses into CA1/subiculum trigger late-onset (>400 ms) firing responses in the medial prefrontal cortex, which are increased after induction of long-term potentiation. Then, we show these responses to be attenuated by optogenetic control of the paraventricular/mediodorsal thalamic area. This suggests that recruitment and plasticity of the hippocampal-prefrontal pathway is partially related to the thalamic-prefrontal loop. When dysfunctional, this interaction may contribute to cognitive deficits, psychotic symptoms, and seizure generalization, which should motivate future studies combining behavioural paradigms and long-range circuit assessment.

Input Convergence, Synaptic Plasticity and Functional Coupling Across Hippocampal-Prefrontal-Thalamic Circuits

“…The beam icon represents intracerebral green light pulses for activation of archaerhodopsins, including on presynaptic terminals. Representative prefrontal cortical data: field potential response with corresponding perievent firing histogram (top; x -axis arrowhead representing afferent stimuli), and theta-filtered voltage trace with corresponding multi-unit activity (bottom; e.g., Hartung et al, 2016 ; Padilla-Coreano et al, 2016 ; Bueno-Junior et al, 2018 ). The latter is also illustrated in the MLT.…”

“…An investigation from our group is an attempt in this direction. Using chronically implanted rats, Bueno-Junior et al ( 2018 ) delivered electrical paired pulses (every 10 s) into the temporal CA1/Sub, while recording single-unit activity and fPSP from mPFC and PV/MD. Paired pulse-locked excitatory responses (<50 ms latency) were found in a proportion of mPFC and PV/MD units, followed by transient suppressions of their activities (160–400 ms latency).…”

“…Particularly in the mPFC, secondary excitatory responses were observed (>400 ms latency), and they were potentiated after LTP induction, i.e., HFS of CA1/Sub. In complementary anesthetized recordings (Bueno-Junior et al, 2018 ), archaerhodopsin-transfected rats received the same implants, except for an optrode in PV/MD. CA1/Sub paired pulses were delivered as in the main experiment, but this time they were randomly accompanied by PV/MD light pulses (50% probability), in order to probe the thalamic role in the CA1/Sub-mPFC recruitment.…”

“…Prior to Bueno-Junior et al ( 2018 ), a series of three studies from one research group reported MD-mPFC input perturbation using chemogenetic (Parnaudeau et al, 2013 ) or optogenetic tools in behaving mice (Padilla-Coreano et al, 2016 ; Bolkan et al, 2017 ). Parnaudeau et al ( 2013 ) used the designer drug clozapine-N-oxide (CNO) to reduce MD firing rate during a behavioral flexibility lever-press task (reversal learning) and a working memory T-maze task (delayed nonmatch-to-sample, DNMS).…”

“…However, behavioral dissections can also probe three- or four-node circuits using stimuli that are sub-threshold for inducing LTP/LTD (e.g., a single pulse/train every 10–30 s). Bueno-Junior et al ( 2018 ) combined these two approaches, though without collecting behavioral data. Electrically-evoked firing responses in the CA1/sub-mPFC pathway (elicited every 10 s) were initially shown to be potentiated by HFS in freely-moving rats.…”