Extrinsic control and autonomous computation in the hippocampal CA1 circuit
In understanding circuit operations, a key issue is the extent to which neuronal spiking reflects local computation or responses to upstream inputs. Because pyramidal cells in CA1 do not have local recurrent projections, it is currently assumed that firing in CA1 is inherited from its inputs – thus, entorhinal inputs provide communication with the rest of the neocortex and the outside world, whereas CA3 inputs provide internal and past memory representations. Several studies have attempted to prove this hypothesis, by lesioning or silencing either area CA3 or the entorhinal cortex and examining the effect of firing on CA1 pyramidal cells. Despite the intense and careful work in this research area, the magnitudes and types of the reported physiological impairments vary widely across experiments. At least part of the existing variability and conflicts is due to the different behavioral paradigms, designs and evaluation methods used by different investigators. Simultaneous manipulations in the same animal or even separate manipulations of the different inputs to the hippocampal circuits in the same experiment are rare. To address these issues, I used optogenetic silencing of unilateral and bilateral mEC, of the local CA1 region, and performed bilateral pharmacogenetic silencing of the entire CA3 region. I combined this with high spatial resolution recording of local field potentials (LFP) in the CA1-dentate axis and simultaneously collected firing pattern data from thousands of single neurons. Each experimental animal had up to two of these manipulations being performed simultaneously. Silencing the medial entorhinal (mEC) largely abolished extracellular theta and gamma currents in CA1, without affecting firing rates. In contrast, CA3 and local CA1 silencing strongly decreased firing of CA1 neurons without affecting theta currents. Each perturbation reconfigured the CA1 spatial map. Yet, the ability of the CA1 circuit to support place field activity persisted, maintaining the same fraction of spatially tuned place fields, and reliable assembly expression as in the intact mouse. Thus, the CA1 network can maintain autonomous computation to support coordinated place cell assemblies without reliance on its inputs, yet these inputs can effectively reconfigure and assist in maintaining stability of the CA1 map.
Spontaneous activity competes with externally evoked responses in sensory cortex
The interaction between spontaneously and externally evoked neuronal activity is fundamental for a functional brain. Increasing evidence suggests that bursts of high-power oscillations in the 15-30 Hz beta-band represent activation of resting state networks and can mask perception of external cues. Yet demonstration of the effect of beta power modulation on perception in real-time is missing, and little is known about the underlying mechanism. In this talk I will present the methods we developed to fill this gap together with our recent results. We used a closed-loop stimulus-intensity adjustment system based on online burst-occupancy analyses in rats involved in a forepaw vibrotactile detection task. We found that the masking influence of burst-occupancy on perception can be counterbalanced in real-time by adjusting the vibration amplitude. Offline analysis of firing-rates and local field potentials across cortical layers and frequency bands confirmed that beta-power in the somatosensory cortex anticorrelated with sensory evoked responses. Mechanistically, bursts in all bands were accompanied by transient synchronization of cell assemblies, but only beta-bursts were followed by a reduction of firing-rate. Our closed loop approach reveals that spontaneous beta-bursts reflect a dynamic state that competes with external stimuli.
Global AND Scale-Free? Spontaneous cortical dynamics between functional networks and cortico-hippocampal communication
Recent advancements in anatomical and functional imaging emphasize the presence of whole-brain networks organized according to functional and connectivity gradients, but how such structure shapes activity propagation and memory processes still lacks asatisfactory model. We analyse the fine-grained spatiotemporal dynamics of spontaneous activity in the entire dorsal cortex. through simultaneous recordings of wide-field voltage sensitive dye transients (VS), cortical ECoG, and hippocampal LFP in anesthetized mice. Both VS and ECoG show cortical avalanches. When measuring avalanches from the VS signal, we find a major deviation of the size scaling from the power-law distribution predicted by the criticality hypothesis and well approximated by the results from the ECoG. Breaking from scale-invariance, avalanches can thus be grouped in two regimes. Small avalanches consists of a limited number of co-activation modes involving a sub-set of cortical networks (related to the Default Mode Network), while larger avalanches involve a substantial portion of the cortical surface and can be clustered into two families: one immediately preceded by Retrosplenial Cortex activation and mostly involving medial-posterior networks, the other initiated by Somatosensory Cortex and extending preferentially along the lateral-anterior region. Rather than only differing in terms of size, these two set of events appear to be associated with markedly different brain-wide dynamical states: they are accompaniedby a shift in the hippocampal LFP, from the ripple band (smaller) to the gamma band (larger avalanches), and correspond to opposite directionality in the cortex-to-hippocampus causal relationship. These results provide a concrete description of global cortical dynamics, and shows how cortex in its entirety is involved in bi-directional communication in the hippocampus even in sleep-like states.