Olfactory Reciprocal Synapses: Dendritic Signaling in the CNS

AbstractSynaptic transmission between dendrites in the olfactory bulb is thought to play a major role in the processing of olfactory information. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAergic dendrodendritic inhibition back onto mitral dendrites. We examined the mechanisms governing reciprocal dendritic transmission in rat olfactory bulb slices. We find that NMDA receptors play a critical role in this dendrodendritic inhibition. As with axonic synapses, the dendritic release of fast neurotransmitters relies on N- and P/Q-type calcium channels. The magnitude of dendrodendritic transmission is directly proportional to dendritic calcium influx. Furthermore, recordings from pairs of mitral cells show that dendrodendritic synapses can mediate lateral inhibition independently of axonal action potentials

Arousal regulates frequency tuning in primary auditory cortex.

Changes in arousal influence cortical sensory representations, but the synaptic mechanisms underlying arousal-dependent modulation of cortical processing are unclear. Here, we use 2-photon Ca2+ imaging in the auditory cortex of awake mice to show that heightened arousal, as indexed by pupil diameter, broadens frequency-tuned activity of layer 2/3 (L2/3) pyramidal cells. Sensory representations are less sparse, and the tuning of nearby cells more similar when arousal increases. Despite the reduction in selectivity, frequency discrimination by cell ensembles improves due to a decrease in shared trial-to-trial variability. In vivo whole-cell recordings reveal that mechanisms contributing to the effects of arousal on sensory representations include state-dependent modulation of membrane potential dynamics, spontaneous firing, and tone-evoked synaptic potentials. Surprisingly, changes in short-latency tone-evoked excitatory input cannot explain the effects of arousal on the broadness of frequency-tuned output. However, we show that arousal strongly modulates a slow tone-evoked suppression of recurrent excitation underlying lateral inhibition [H. K. Kato, S. K. Asinof, J. S. Isaacson, Neuron, 95, 412-423, (2017)]. This arousal-dependent "network suppression" gates the duration of tone-evoked responses and regulates the broadness of frequency tuning. Thus, arousal can shape tuning via modulation of indirect changes in recurrent network activity

Network-Level Control of Frequency Tuning in Auditory Cortex

Lateral inhibition is a fundamental circuit operation that sharpens the tuning properties of cortical neurons. This operation is classically attributed to an increase in GABAergic synaptic input triggered by non-preferred stimuli. Here we use in vivo whole-cell recording and two-photon Ca imaging in awake mice to show that lateral inhibition shapes frequency tuning in primary auditory cortex via an unconventional mechanism: non-preferred tones suppress both excitatory and inhibitory synaptic inputs onto layer 2/3 cells ("network suppression"). Moreover, optogenetic inactivation of inhibitory interneurons elicits a paradoxical increase in inhibitory synaptic input. These results indicate that GABAergic interneurons regulate cortical activity indirectly via the suppression of recurrent excitation. Furthermore, the network suppression underlying lateral inhibition was blocked by inactivation of somatostatin-expressing interneurons (SOM cells), but not parvalbumin-expressing interneurons (PV cells). Together, these findings reveal that SOM cells govern lateral inhibition and control cortical frequency tuning through the regulation of reverberating recurrent circuits

Fear Learning Regulates Cortical Sensory Representations by Suppressing Habituation

Projections from auditory cortex to the amygdala are thought to contribute to the induction of auditory fear learning. In addition, fear conditioning has been found to enhance cortical responses to conditioned tones, suggesting that cortical plasticity contributes to fear learning. However, the functional role of auditory cortex in the retrieval of fear memories is unclear and how fear learning regulates cortical sensory representations is not well understood. To address these questions, we use acute optogenetic silencing and chronic two-photon calcium imaging in mouse auditory cortex during fear learning. Longitudinal imaging of neuronal ensemble activity reveals that discriminative fear learning modulates cortical sensory representations via the suppression of cortical habituation

How Inhibition Shapes Cortical Activity

Cortical processing reflects the interplay of synaptic excitation and synaptic inhibition. Rapidly accumulating evidence is highlighting the crucial role of inhibition in shaping spontaneous and sensory-evoked cortical activity and thus underscores how a better knowledge of inhibitory circuits is necessary for our understanding of cortical function. We discuss current views of how inhibition regulates the function of cortical neurons and point to a number of important open questions

Counting quanta: Direct measurements of transmitter release at a central synapse

AbstractContradictory hypotheases regarding the nature of synaptic transmission in the CNS have arisen from indirect methods of quantal analysis. In this study, we directly count the quanta released following nerve stimulation to examine synaptic transmission at a fast glutamatergic synapse in the mammalian auditory brainstem. Our results demonstrate the relationship between spontaneous and nerve-evoked synaptic events, indicate that asynchronous transmitter release governs the time course of evoked transmission, and show that the stochastic quantal release process, as originally proposed at the neuromuscular junction, is highly conserved at this central synapse

Linking neuronal ensembles by associative synaptic plasticity.

Synchronized activity in ensembles of neurons recruited by excitatory afferents is thought to contribute to the coding information in the brain. However, the mechanisms by which neuronal ensembles are generated and modified are not known. Here we show that in rat hippocampal slices associative synaptic plasticity enables ensembles of neurons to change by incorporating neurons belonging to different ensembles. Associative synaptic plasticity redistributes the composition of different ensembles recruited by distinct inputs such as to specifically increase the similarity between the ensembles. These results show that in the hippocampus, the ensemble of neurons recruited by a given afferent projection is fluid and can be rapidly and persistently modified to specifically include neurons from different ensembles. This linking of ensembles may contribute to the formation of associative memories