Synaptic mechanisms of top-down control in the non-lemniscal inferior colliculus

Abstract

Corticofugal projections to evolutionarily ancient, subcortical structures are ubiquitous across mammalian sensory systems. These ‘descending’ pathways enable the neocortex to control ascending sensory representations in a predictive or feedback manner, but the underlying cellular mechanisms are poorly understood. Here, we combine optogenetic approaches with in vivo and in vitro patch-clamp electrophysiology to study the projection from mouse auditory cortex to the inferior colliculus (IC), a major descending auditory pathway that controls IC neuron feature selectivity, plasticity, and auditory perceptual learning. Although individual auditory cortico-collicular synapses were generally weak, IC neurons often integrated inputs from multiple corticofugal axons that generated reliable, tonic depolarizations even during prolonged presynaptic activity. Latency measurements in vivo showed that descending signals reach the IC within 30 ms of sound onset, which in IC neurons corresponded to the peak of synaptic depolarizations evoked by short sounds. Activating ascending and descending pathways at latencies expected in vivo caused a NMDA receptor-dependent, supralinear excitatory postsynaptic potential summation, indicating that descending signals can nonlinearly amplify IC neurons’ moment-to-moment acoustic responses. Our results shed light upon the synaptic bases of descending sensory control and imply that heterosynaptic cooperativity contributes to the auditory cortico-collicular pathway’s role in plasticity and perceptual learning.

Recurrent circuits amplify corticofugal signals and drive feedforward inhibition in the inferior colliculus

“…In n = 4 neurons, repetitive auditory cortical activity (80 stimuli at 20 Hz) caused a tonic or phasic hyperpolarization of the membrane potential (Figure 1F), whereas in 1 neuron tested, single light flashes generated a single, long-latency IPSP. Altogether these data indicate that in addition to the monosynaptic depolarizations mediated by glutamatergic corticofugal projections (Oberle et al, 2022), descending activity can also substantially hyperpolarize IC neurons, presumably via polysynaptic inhibition.…”

“…Our virus injection protocol is described in detail in Oberle et al, 2022. Briefly, mice were anesthetized with 4-5% isoflurane in O 2 , mounted in a stereotaxic frame, and isoflurane was lowered to 1-2% while body temperature was maintained near 37-38° C using a heating blanket.…”

“…The raw data from some of these in vivo recordings were also included in a previous set of distinct analyses (Oberle et al, 2022). Surgery for intracranial virus injections: Our virus injection protocol is described in detail in Oberle et al, 2022. Briefly, mice were anesthetized with 4-5% isoflurane in O2, mounted in a stereotaxic frame, and isoflurane was lowered to 1-2% while body temperature was maintained near 37-38° C using a heating blanket.…”

“…A post-operative dose of carprofen was administered ~24 hours later. In vivo electrophysiology: Mice were deeply anesthetized with isoflurane, mounted in the stereotaxic frame, and craniotomies were carefully opened over the left IC and auditory cortex as described above and in Oberle et al 2022. For optogenetic stimulation, we left the dura intact and implanted a cranial window over the auditory cortex.…”

“…We used patch-clamp electrophysiology and optogenetics in brain slices from fluorescent GABA reporter mice to study corticofugal transmission onto identified IC neurons. We focused specifically on neurons in the dorso-medial “shell” IC because this sub-region receives the densest projection of corticofugal axons (Winer et al, 1998; Song et al, 2018; Oberle et al, 2022). Our data confirm previous anatomical predictions by showing that corticofugal transmission is on average stronger onto shell IC glutamate compared to GABA neurons.…”