Cell-Specific Activity-Dependent Fractionation of Layer 2/3→5B Excitatory Signaling in Mouse Auditory Cortex

Abstract

Auditory cortex (AC) layer 5B (L5B) contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. Although it is known that these neuronal types have distinct roles in auditory processing and different response properties to sound, the synaptic and intrinsic mechanisms shaping their input-output functions remain less understood. Here, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B. Corticocollicular neurons had, on average, lower input resistance, greater hyperpolarization-activated current (I h ), depolarized resting membrane potential, faster action potentials, initial spike doublets, and less spike-frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, the probabilities of connection, amplitude, latency, rise time, and decay time constant of the unitary EPSC were not different for L2/3¡corticocollicular and L2/3¡corticocallosal connections. However, short trains of unitary EPSCs showed no synaptic depression in L2/3¡corticocollicular connections, but substantial depression in L2/3¡corticocallosal connections. Synaptic potentials in L2/3¡corticocollicular connections decayed faster and showed less temporal summation, consistent with increased I h in corticocollicular neurons, whereas synaptic potentials in L2/3¡corticocallosal connections showed more temporal summation. Extracellular L2/3 stimulation at two different rates resulted in spiking in L5B neurons; for corticocallosal neurons the spike rate was frequency dependent, but for corticocollicular neurons it was not. Together, these findings identify cell-specific intrinsic and synaptic mechanisms that divide intracortical synaptic excitation from L2/3 to L5B into two functionally distinct pathways with different input-output functions.

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“…6A, Left). We previously confirmed that retrogradely labeled layer 2/3 corticocallosal and layer 5B corticocollicular neurons in this manner consistently overlay the functionally localized auditory cortex (43,44). Local stimulation to layer 2/3 was used to evoke excitatory postsynaptic currents (EPSCs) in retrogradely labeled layer 2/3 corticocallosal neurons (Fig.…”

“…Nonetheless, we deemed it necessary to evalu-ate the possibility that cpd5 has nonspecific effects on neuronal synaptic and intrinsic properties. For this purpose, we evaluated the effects of 10 μM cpd5 on the synaptic and intrinsic properties of 2 distinct populations of projection neurons in the mouse auditory cortex: the layer 2/3 corticocallosal neurons projecting to the contralateral auditory cortex and the layer 5B corticocollicular neurons projecting to the ipsilateral inferior colliculus (43,44). Along with being guided by anatomic landmarks such as the rhinal fissure and the hippocampal anatomy to locate the auditory cortex, we injected green retrograde fluorospheres in the contralateral cortex and red retrograde fluorospheres in the ipsilateral inferior colliculus to label the layer 2/3 corticocallosal and layer 5B corticocollicular neuronal populations, respectively (Fig.…”

Superficial Layers Suppress the Deep Layers to Fine-tune Cortical Coding

“…In some L5 units (ϳ40%), we observed no significant change in firing rate while manipulating L2/3. This result is expected given that different subtypes of L5 neurons integrate divergent streams of input, sometimes preferentially from either subcortical or long-range cortical areas (Wright and Fox, 2010;Mao et al, 2011;Joshi et al, 2015;Kim et al, 2015;Kinnischtzke et al, 2016). Technological innovations that combine trans-synaptic labeling of projection neurons, multiphoton imaging of deep tissue, and layer-specific optogenetic manipulations could determine whether long-range connectivity patterns predict functional relationships within the intracortical microcircuit.…”

Frequency-dependent gating of feedforward inhibition in thalamofrontal synapses

“…4G, H and Supplementary Figure 1B). We attributed the dramatic reduction of AP generation to a relatively high rheobase of PV neurons in the cortices [27,28]. The observed failure in AP generation was not due to ChR2 inactivation, as optogenetic 10 Hz stimulation evoked immediate and reliable APs in ChR2-expressing MD neurons in our experimental condition (data not shown).…”