Biology subjects

Clem, R. L.

Publications and source records attributed to Clem, R. L..

3 recordsLinked to original sources

bioRxiv2021

Ensemble encoding of conditioned fear by prefrontal somatostatin interneurons

Neurons preferentially activated by learning have been ascribed the unique potential to encode memory. However, it remains unclear which genetically-defined cell types are recruited as part of such an ensemble, or what role discrete subpopulations play in behavior. Here we show that fear conditioning activates a heterogeneous neural ensemble in the medial prefrontal cortex (mPFC), comprised to a large degree of GABAergic interneurons immunoreactive for somatostatin (SST-INs). Using an intersectional genetic approach, we demonstrate that fear learning-activated SST-INs exhibit distinct circuit properties, are preferentially reactivated during memory retrieval, and mediate the expression of defensive freezing. We further show that a rewarding experience, morphine treatment, activates an orthogonal SST-IN population that exerts opposing control over fear. These results outline an important role for discrete GABAergic ensembles in fear memory encoding, and point to an unappreciated capacity for functional specialization among SST-INs.

neuroscience↗

bioRxiv2020

An adolescent sensitive period of heightened frontal top-down projection activity promotes local circuit integration and attentional behavior

Frontal top-down cortical neurons projecting to sensory cortical regions are well-positioned to integrate long-range inputs with local circuitry in frontal cortex to implement top-down attentional control of sensory regions. How adolescence contributes to the maturation of top-down neurons and associated local/long-range input balance, and the establishment of attentional control is poorly understood. Here we combine projection-specific electrophysiological and rabies-mediated input mapping in mice to uncover adolescence as a developmental stage when frontal top-down neurons projecting from the anterior cingulate to visual cortex are highly functionally integrated into local excitatory circuitry and have heightened activity compared to adulthood. Chemogenetic suppression of top-down neuron activity selectively during adolescence, but not later periods, produces long-lasting visual attentional behavior deficits, and results in excessive loss of local excitatory inputs in adulthood. Our study reveals an adolescent sensitive period when top-down neurons integrate local circuits with long-range connectivity to produce attentional behavior.

neuroscience↗

bioRxiv2019

Prefrontal somatostatin interneurons encode fear memory

Theories stipulate that memories are encoded within networks of cortical projection neurons (PNs). Conversely, GABAergic interneurons (INs) are thought to function primarily to inhibit PNs and thereby impose network gain control, an important but purely modulatory role. However, we found that associative fear learning potentiates synaptic transmission and cue-specific activity of medial prefrontal cortex (mPFC) somatostatin interneurons (SST-INs), and that activation of these cells controls both memory encoding and expression. Furthermore, the synaptic organization of SST- and parvalbumin (PV)-INs provides a potential circuit basis for SST-IN-evoked disinhibition of mPFC output neurons and recruitment of remote brain regions associated with defensive behavior. These data suggest that rather than constrain mnemonic processing, potentiation of SST-IN activity represents an important causal mechanism for conditioned fear.

neuroscience↗