Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons

Abstract

Corticothalamic (CT) feedback plays an important role in regulating the sensory information that the cortex receives. Within the somatosensory cortex layer VI originates the feedback to the ventral posterior medial (VPM) nucleus of the thalamus, which in turn receives sensory information from the contralateral whiskers. We examined the physiology and morphology of CT neurons in rat somatosensory cortex, focusing on the physiological characteristics of the monosynaptic inputs that they receive from the thalamus. To identify CT neurons, rhodamine microspheres were injected into VPM and allowed to retrogradely transport to the soma of CT neurons. Thalamocortical slices were prepared at least 3 days post injection. Whole-cell recordings from labeled CT cells in layer VI demonstrated that they are regular spiking neurons and exhibit little spike frequency adaption. Two anatomical classes were identified based on their apical dendrites that either terminated by layer V (compact cells) or layer IV (elaborate cells). Thalamic inputs onto identified CT-VPM neurons demonstrated paired pulse depression over a wide frequency range (2-20 Hz). Stimulus trains also resulted in significant synaptic depression above 10 Hz. Our results suggest that thalamic inputs differentially impact CT-VPM neurons in layer VI. This characteristic may allow them to differentiate a wide range of stimulation frequencies which in turn further tune the feedback signals to the thalamus.

Infrabarrels Are Layer 6 Circuit Modules in the Barrel Cortex that Link Long-Range Inputs and Outputs

“…During trains of stimulation, both the excitatory VPm and POm responses in L6 underwent similar short-term depression, a frequently described feature of thalamcortical synapses (Beierlein and Connors, 2002; Cruikshank et al, 2010; Gabernet et al, 2005; Yang et al, 2014). Moreover, we found that local synaptic connections between CT and CC neurons are relatively sparse and not reciprocal, consistent with previous work in the sensory cortex of different species (Beierlein and Connors, 2002; Lefort et al, 2009; Mercer et al, 2005).…”

“…Previous studies showed that L6 CT and CC neurons exhibit distinctive intrinsic properties, including excitability (Brumberg et al, 2003; Kinnischtzke et al, 2016; Kumar and Ohana, 2008; Velez-Fort et al, 2014; Yang et al, 2014), however the results of these studies differed substantially. Clarifying these differences is critical for understanding L6 circuit mechanisms.…”

“…Barrel cortex receives two main types of somatosensory inputs that originate from different thalamic nuclei, the ventral posterior medial nucleus (VPm) and the posterior medial nucleus (POm) (Chmielowska et al, 1989; Wimmer et al, 2010). While many studies have examined the impact of these pathways on barrel cortex, they either overlook L6, fail to identify the postsynaptic cell types in L6, or use non-specific electrical stimulation to activate thalamic axons (Audette et al, 2017; Beierlein and Connors, 2002; Bureau et al, 2006; Cruikshank et al, 2010; Petreanu et al, 2009; Yang et al, 2014). To investigate pathway-specific responses in distinct classes of L6 excitatory cells, we combined optogenetic control strategies with cell type-specific genetics and whole-cell recordings using an acute in vitro preparation (Agmon and Connors, 1991; Crandall et al, 2015; Cruikshank et al, 2010).…”

“…Neocortical L6 is a principal output layer that has an essential role in modulating both cortical and thalamic activities (Crandall et al, 2015; Denman and Contreras, 2015; Guo et al; Kim et al, 2014; Lam and Sherman, 2010; Li and Ebner, 2007; Mease et al, 2014; Olsen et al, 2012; Temereanca and Simons, 2004). L6 neurons receive direct input from excitatory thalamic relay neurons (Beierlein and Connors, 2002; Constantinople and Bruno, 2013; Cruikshank et al, 2010; Oberlaender et al, 2012; Yang et al, 2014), implying that L6 may play a strategic role in early thalamocortical processing. Among all the cortical layers, L6 also contains the richest diversity of morphologically and physiologically distinct neurons (Briggs, 2010; Briggs et al, 2016; Chen et al, 2009; Kumar and Ohana, 2008; Thomson, 2010; Zhang and Deschenes, 1997).…”

“…Broadly speaking, three main types of L6 neurons can be defined by their axonal projections (Zhang and Deschenes, 1997): excitatory corticothalamic (CT) and corticocortical (CC) projection neurons, and local inhibitory interneurons. The L6 projection neurons differ in their intrinsic properties, dendrite and axon morphologies, long-range inputs and outputs, and in vivo activity patterns (Kumar and Ohana, 2008; Narayanan et al, 2015; Oberlaender et al, 2012; Velez-Fort et al, 2014; Yang et al, 2014); this has led to suggestions that L6 CT and CC cells participate in distinct subcircuits within the infragranular network (Kumar and Ohana, 2008; Velez-Fort et al, 2014). …”