A thalamocortical top-down circuit for associative memory

Abstract

The sensory neocortex is a critical substrate for memory. Despite its strong connection with the thalamus, the role of direct thalamocortical communication in memory remains elusive. We performed chronic in vivo two-photon calcium imaging of thalamic synapses in mouse auditory cortex layer 1, a major locus of cortical associations. Combined with optogenetics, viral tracing, whole-cell recording, and computational modeling, we find that the higher-order thalamus is required for associative learning and transmits memory-related information that closely correlates with acquired behavioral relevance. In turn, these signals are tightly and dynamically controlled by local presynaptic inhibition. Our results not only identify the higher-order thalamus as a highly plastic source of cortical top-down information but also reveal a level of computational flexibility in layer 1 that goes far beyond hard-wired connectivity.

Bottom-up inputs are required for the establishment of top-down connectivity onto cortical layer 1 neurogliaform cells

“…Importantly, the fact that L1 cINs have been shown to receive both thalamic (Ji, Zingg et al 2015) and inter-cortical connections (Leinweber, Ward et al 2017) ideally positions them to modulate incoming sensory inputs and affect excitatory responses (Zhu and Zhu 2004, Jiang, Wang et al 2013, Lee, Wang et al 2015, Anastasiades, Collins et al 2020). L1 cINs have been shown to play a role in, cross-modal integration (Ibrahim, Mesik et al 2016), interhemispheric integration (Palmer, Schulz et al 2012), associative fear learning and plasticity (Abs, Poorthuis et al 2018, Pardi, Vogenstahl et al 2020) as well as sensory motor integration (Mesik, Huang et al 2019). This makes L1 cINs a likely important target for the integration of bottom-up and top-down signaling.…”

Corticothalamic Pathways in Auditory Processing: Recent Advances and Insights From Other Sensory Systems

“…However, there is still no direct evidence that such transthalamic top-down, modulatory pathways exist. Evidence exists that higher order thalamic nuclei provide modulator inputs to first order, primary cortical areas in visual (Purushothaman et al, 2012 ; Roth et al, 2016 ), somatosensory (Viaene et al, 2011 ) and auditory systems (Pardi et al, 2020 ). Because modulation is provided by a higher order thalamic nucleus to a lower order cortical area, these circuits can be viewed as descending, top-down circuits.…”

“…Because modulation is provided by a higher order thalamic nucleus to a lower order cortical area, these circuits can be viewed as descending, top-down circuits. Using a combination of optogenetics, whole-cell recordings, behavior, and computational modeling, Pardi et al ( 2020 ) identified an auditory top-down circuit that conveys information about the experience-dependent behavioral relevance of sounds from higher order auditory thalamus (all nuclei surrounding the MGV) to layer 1 in primary auditory cortex (anatomical evidence for this pathway in classical studies: Lorente de No, 1938 ; Malmierca et al, 2002 ). Interestingly, synaptic transmission in A1 is in turn modulated by local inhibition acting on GABAB receptors at the presynaptic thalamic terminal.…”

“…Interestingly, synaptic transmission in A1 is in turn modulated by local inhibition acting on GABAB receptors at the presynaptic thalamic terminal. Because higher order thalamic neurons that specifically project to A1 receive inputs from a diversity of higher order cortical areas (e.g., secondary auditory and association cortices), the top-down circuit identified by Pardi et al ( 2020 ) might well be part of a transthalamic feedback circuit that conveys internally generated top-down signals. At the thalamic node, these top-down signals have the chance to be integrated and compared with sensory information conveyed by subcortical inputs to A1-projecting thalamic neurons (e.g., superior colliculus and external cortex of the inferior colliculus; Malmierca et al, 2002 ; Cai et al, 2019 ; Pardi et al, 2020 ).…”

“…Such transthalamic feedback pathways would provide modulatory or non-linear context-sensitive effects consistent with the tenets of predictive coding (Friston, 2005 ; Bastos et al, 2012 ). In this context, the fact that synaptic transmission of higher order MGB-A1 neurons synapses can be modulated by local inhibition in L1 as Pardi et al ( 2020 ) demonstrated, is particularly interesting because it provides the computational flexibility that feedback connections require to convey predictions in a context-sensitive manner (Bastos et al, 2012 ; discussed in section Role of Corticothalamic Pathways in the Implementation of Predictive Processing Frameworks).…”