Disinhibition

A long-standing theory proposes memories are stored in the synaptic wiring of strongly connected neural populations, known as neural assemblies. However, experimental evidence for assembly formation has been limited to inferring changes in synaptic connectivity from changes in neural activity following behavioral learning. Using tagged c-fos activity combined with channelrhodopsin expression, we directly measured the synaptic strength between neurons in the Piriform cortex (PCx) following mice learning an odor discrimination task. Our results suggest that an assembly forms after learning, but

Over the years, excitatory neurons received much attention for their role in brain dynamics, while the inhibitory neurons were understood to play more of a support, stabilizing role. However, recent advances have revealed that memories are encoded both by excitatory and inhibitory neurons (EI engrams), adding to the evidence of the functional importance of inhibitory neurons beyond mere stability. Still, the computations enabled by such EI engrams are unclear, and the synaptic plasticity rules that could create and sustain them are unknown. Here, we explore in silico a mechanism for EI engram

Neural activity in the cortex exhibits a wide range of timescales, allowing animals to respond to rapidly changing sensory stimuli while maintaining information in working memory. Recent studies show how top-down inputs representing locomotive state modulates these timescales differently across visual areas in mice. In particular, the sign of correlations between speed and neural activity varies by region, highlighting the interplay between bottom-up sensory inputs, top-down pathways and connectivity motifs in shaping cortical dynamics. In addition, cortical circuits comprise a large diversity

Neural activity in the cortex exhibits a wide range of timescales, allowing animals to respond to rapidly changing sensory stimuli while maintaining information in working memory. The timescales of neural activity are not only affected by bottom-up sensory inputs, but also by top-down inputs originating from corticocortical and neuromodulatory pathways. In addition, cortical circuits comprise a large diversity of cell types connected in non-random ways, which are the subject of profound plasticity dynamics. Due to this complexity, understanding how top-down projections affect the timescales of

The brain continuously encodes new information as memories. At the synaptic level, memory formation is enabled by adjusting connections between activated excitatory neurons in the cortex, with mirroring inhibitory activity ensuring stable storage. Particularly, synaptic plasticity occurs as memory reactivation takes place during sleep, contributing to increased memory stability. However, the mechanism by which reactivation mediates plasticity to balance network currents for stable memory storage remains unclear. Here, we investigated whether a newly proposed form of codependent plasticity coul

…Here, we investigated whether disinhibition could play a major role in this process. Using optogenetic behavioral experiments we found that when fear was associated with the inhibition of mouse hippocampal somatostatin positive interneurons, the re-inhibition of the same interneurons could

Network models of cortex typically focus on excitatory population dynamics, relegating inhibition to a support role. However, recent studies have shown that memories can be encoded by both excitatory and inhibitory neurons (EI engrams), adding to the evidence of the functional importance of inhibitory neurons beyond mere stabilization. The functional consequence of such EI engrams is unclear, and the synaptic plasticity rules that could sustain them are unknown. Here, we explore in silico a mechanism for EI engrams storage and recall to glean possible computational benefits of such engrams ove

…Disinhibition, caused by the synaptic inhibition of inhibitory neurons by other inhibitory neurons, increases the excitability of principal neurons and has been proposed as a contributing factor in numerous neurological diseases, including epilepsy. Therefore, unravelling inhibitory microcircuits in the piriform cortex may uncover new therapeutic avenues for treating epilepsy. Our study used whole-cell recordings from identified classes of inhibitory in

Although distinct cortical regions specialize in different functions, they also benefit from receiving global reinforcement feedback to tune local processing. When and how those reinforcement signals shape cortical computations remains however largely unknown. Here, we present experimental evidence showing that acetylcholine inputs throughout the cortex form the backbone for a global signal, that presents the main characteristic of an unsigned reinforcement prediction error computation : modulation of the reinforcement response by expectation and coding of predictive cues. We show that this gl

Sequenced behaviors, including locomotion, reaching, and vocalization, are patterned differently in different contexts, enabling animals to adjust to their current environments. However, how contextual information shapes neural activity to flexibly alter action patterning is not yet understood. Prior work indicates such flexibility could be achieved via parallel motor circuits, with differing sensitivities to sensory context; instead we demonstrate here how a single neural pathway operates in two different regimes dependent on recent sensory history. We leverage the Drosophila song production

Animals depend on fast and reliable detection of novel stimuli in their environment. Neurons in multiple sensory areas respond more strongly to novel in comparison to familiar stimuli. Yet, it remains unclear which circuit, cellular, and synaptic mechanisms underlie those responses. Here, we show that spike-timing-dependent plasticity of inhibitory-to-excitatory synapses generates novelty responses in a recurrent spiking network model. Inhibitory plasticity increases the inhibition onto excitatory neurons tuned to familiar stimuli, while inhibition for novel stimuli remains low, leading to a n

The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Recent experiments showed that repeated cholinergic activation of 𝛼7 nACh receptors expressed in oriens-lacunosum-moleculare (OLM𝛼2) interneurons could induce LTP in SC-CA1 synapses. We used a biophysically realistic computational model to examine mechanistically how cholinergic activation of OLMa2 interneurons increases SC to CA1 transmission. Our results suggest t

Sensory experience and perceptual learning changes receptive field properties of cortical pyramidal neurons possibly mediated by long-term potentiation (LTP) of synapses. We have previously shown in the mouse somatosensory cortex (S1) that sensory-driven LTP in layer (L) 2/3 pyramidal neurons is dependent on higher order thalamic feedback from the posteromedial nucleus (POm), which is thought to convey contextual information from various cortical regions integrated with sensory input. We have followed up on this work by dissecting the cortical microcircuitry that underlies this form of LTP

Mammalian babies are “sensory traps” for parents. Various sensory cues from the newborn are tremendously efficient in triggering parental responses in caregivers. We recently showed that core aspects of maternal behavior such as pup retrieval in response to infant vocalizations rely on active learning of auditory cues from pups facilitated by the neurohormone oxytocin (OT). Release of OT from the hypothalamus might thus help induce recognition of different infant cues but it is unknown what sensory stimuli can activate OT neurons. I performed unprecedented in vivo whole-cell and cell-attached

…behavioural tasks due to circuit disinhibition, has recently arisen as an important and conserved processing motif. It has been also recognized that, in cortical circuits, a subpopulation of GABAergic cells that express vasoactive intestinal polypeptide (VIP) innervates selectively inhibitory interneurons, providing for circuit disinhibition as a possible outcome, depending on the network state and behavioural context. In this talk, I will highlight the latest discoveries