A Novel Biophysical Model for the Generation of Sharp Wave Ripples in CA1 Hippocampus.

Synchronous activities among neurons in the brain generate emergent network oscillations such as the hippocampal Sharp-wave ripples (SPWRs) that facilitate information processing during memory formation. However, how neurons and circuits are functionally organized to generate oscillations remains unresolved. Biophysical models of neuronal networks can shed light on how thousands of neurons interact in intricate circuits to generate such emergent SPWR network events. Here we developed a large-scale biophysically realistic neural network model of CA1 hippocampus with functionally organized circuit modules containing distinct types of neurons. Model simulations reproduced synaptic, cellular and network aspects of physiological SPWRs. The model provided insights into the role of neuronal types and their microcircuit motifs in generating SPWRs in the CA1 region. The model also suggests experimentally testable predictions including the role of specific neuron types in the genesis of hippocampal SPWRs.

High-fidelity dendritic sodium spike generation in human layer 2/3 neocortical pyramidal neurons.

Dendritic spikes function as cardinal components of rodent neocortical circuit computations. Recently, the biophysical properties of human pyramidal neurons (PNs) have been reported to be divergent, raising the question of whether dendritic spikes have homologous roles in the human neocortex. To directly address this, we made electrical recordings from the soma and apical dendrites of human and rat layer 2/3 PNs of the temporal cortex. In both species, dendritic excitatory input led to the initiation of sodium-channel-mediated dendritic spikes. Dendritic sodium spikes could be generated across a wide input range, exhibited a similar frequency range of activation, and forward-propagated with high-fidelity to implement stereotyped computations in human and rat PNs. However, the physical expansion and complexification of the apical dendritic trees of human PNs allowed the enriched expression of dendritic spike generation. The computational capacity of human PNs is therefore enhanced by the widespread implementation of a conserved dendritic integration mechanism.

A protocol to investigate cellular and circuit mechanisms generating sharp wave ripple oscillations in rodent basolateral amygdala using ex vivo slices.

Basolateral amygdala circuits generate oscillatory network activity to process and remember emotion-tagged events. Ex vivo preparations that recapitulate network activities seen in vivo provide an ideal system to investigate the mechanisms driving these network oscillations. Here we describe an ex vivo preparation of basolateral amygdala slices from rodents for measuring the generated sharp wave ripple oscillations (SWs) using local field potential recording and targeted recording from chandelier neurons that initiate SWs. For complete details on the use and execution of this protocol, please refer to Perumal et al. (2021).

Inhibitory Circuits in the Basolateral Amygdala in Aversive Learning and Memory.

Neural circuits in the basolateral amygdala (BLA) play a pivotal role in the learning and memory formation, and processing of emotionally salient experiences, particularly aversive ones. A diverse population of GABAergic neurons present in the BLA orchestrate local circuits to mediate emotional memory functions. Targeted manipulation of GABAergic neuronal subtypes has shed light on cell-type specific functional roles in the fear learning and memory, revealing organizing principles for the operation of inhibitory circuit motifs in the BLA.

Microcircuit mechanisms for the generation of sharp-wave ripples in the basolateral amygdala: A role for chandelier interneurons.

Synchronized activity in neural circuits, detected as oscillations in the extracellular field potential, has been associated with learning and memory. Neural circuits in the basolateral amygdala (BLA), a mid-temporal lobe structure, generate oscillations in specific frequency bands to mediate emotional memory functions. However, how BLA circuits generate oscillations in distinct frequency bands is not known. Of these, sharp-waves (SWs) are repetitive, brief transitions that contain a low-frequency (<20 Hz) envelope, often coupled with ripples (100-300 Hz), have been associated with memory consolidation. Here, we show that SWs are retained in the BLA ex vivo and generated by local circuits. We demonstrate that an action potential in a chandelier interneuron is sufficient to initiate SWs through local circuits. Using a physiologically constrained model, we show that microcircuits organized as chandelier-interneuron-driven modules reproduce SWs and associated cellular events, revealing a functional role for chandelier interneurons and microcircuits for SW generation.

Development and physiology of GABAergic feedback excitation in parvalbumin expressing interneurons of the mouse basolateral amygdala.

We have previously shown that in the basolateral amygdala (BLA), action potentials in one type of parvalbumin (PV)-expressing GABAergic interneuron can evoke a disynaptic feedback excitatory postsynaptic potential (fbEPSP) onto the same presynaptic interneuron. Here, using whole-cell recordings from PV-expressing interneurons in acute brain slices we expand on this finding to show that this response is first detectable at 2-week postnatal, and is most prevalent in animals beyond 3 weeks of age (>P21). This circuit has a very high fidelity, and single action potential evoked fbEPSPs display few failures. Reconstruction of filled neurons, and electron microscopy show that interneurons that receive feedback excitation make symmetrical synapses on both the axon initial segments (AIS), as well as the soma and proximal dendrites of local pyramidal neurons, suggesting fbEPSP interneurons are morphologically distinct from the highly specialized chandelier neurons that selectively target the axon initial segment of pyramidal neurons. Single PV interneurons could trigger very large (~ 1 nA) feedback excitatory postsynaptic currents (fbEPSCs) suggesting that these neurons are heavily reciprocally connected to local glutamatergic principal cells. We conclude that in the BLA, a subpopulation of PV interneurons forms a distinct neural circuit in which a single action potential can recruit multiple pyramidal neurons to discharge near simultaneously and feed back onto the presynaptic interneuron.