A cultured neuron probe

Work in progress toward the creation of a "cultured neuron probe" is described. This is a silicon structure similar to that for a multielectrode probe, but with embedded neurons which are intended to grow out and integrate with the neurons of a host nervous system into which the probe has been inserted. Each probe neuron is in close proximity to an electrode which is designed for extracellular estimation and recording from the probe neuron. In this way the probe neurons may provide a highly specific long-term communication link between external electronics and the host. Initial experiments to establish the feasibility of the concept will be done in rat hippocampus

A cultured neuron probe

Work in progress toward the creation of a "cultured neuron probe" is described. This is a silicon structure similar to that for a multielectrode probe, but with embedded neurons which are intended to grow out and integrate with the neurons of a host nervous system into which the probe has been inserted. Each probe neuron is in close proximity to an electrode which is designed for extracellular estimation and recording from the probe neuron. In this way the probe neurons may provide a highly specific long-term communication link between external electronics and the host. Initial experiments to establish the feasibility of the concept will be done in rat hippocampus

Cell Assembly Sequences Arising from Spike Threshold Adaptation Keep Track of Time in the Hippocampus

Hippocampal neurons can display reliable and long-lasting sequences of transient firing patterns, even in the absence of changing external stimuli. We suggest that time-keeping is an important function of these sequences, and propose a network mechanism for their generation. We show that sequences of neuronal assemblies recorded from rat hippocampal CA1 pyramidal cells can reliably predict elapsed time (15–20 s) during wheel running with a precision of 0.5 s. In addition, we demonstrate the generation of multiple reliable, long-lasting sequences in a recurrent network model. These sequences are generated in the presence of noisy, unstructured inputs to the network, mimicking stationary sensory input. Identical initial conditions generate similar sequences, whereas different initial conditions give rise to distinct sequences. The key ingredients responsible for sequence generation in the model are threshold-adaptation and a Mexican-hat-like pattern of connectivity among pyramidal cells. This pattern may arise from recurrent systems such as the hippocampal CA3 region or the entorhinal cortex.Wehypothesize that mechanisms that evolved for spatial navigation also support tracking of elapsed time in behaviorally relevant contexts

Cell-type- and activity-dependent extracellular correlates of intracellular spiking

Despite decades of extracellular action potential (EAP) recordings monitoring brain activity, the biophysical origin and inherent variability of these signals remains enigmatic. We performed whole-cell patch recordings of excitatory and inhibitory neurons in rat somatosensory cortex slice while positioning a silicon probe in their vicinity to concurrently record intra- and extracellular voltages for spike frequencies under 20 Hz. We characterize biophysical events and properties (intracellular spiking, extracellular resistivity, temporal jitter, etc.) related to EAP-recordings at the single-neuron level in a layer-specific manner. EAP-amplitude was found to decay as the inverse of distance between the soma and the recording electrode with similar (but not identical) resistivity across layers. Furthermore, we assessed a number of EAP-features and their variability with spike activity: amplitude (but not temporal) features varied substantially (approx. 30-50% compared to mean) and non-monotonically as a function of spike frequency and spike order. Such EAP-variation only partly reflects intracellular somatic spike variability and points to the plethora of processes contributing to the EAP. Also, we show that the shape of the EAP-waveform is qualitative similar to the negative of the temporal derivative to the intracellular somatic voltage - as expected from theory. Finally, we tested to what extent EAPs can impact the lowpass filtered part of extracellular recordings, the local field potential (LFP), typically associated with synaptic activity. We found that spiking of excitatory neurons can significantly impact the LFP at frequencies as low as 20 Hz. Our results question the common assertion that LFPs act as proxy for synaptic activity

A Miniaturized 256-Channel Neural Recording Interface With Area-Efficient Hybrid Integration of Flexible Probes and CMOS Integrated Circuits

We report a miniaturized, minimally invasive high-density neural recording interface that occupies only a 1.53 mm(2) footprint for hybrid integration of a flexible probe and a 256-channel integrated circuit chip. To achieve such a compact form factor, we developed a custom flip-chip bonding technique using anisotropic conductive film and analog circuit-under-pad in a tiny pitch of 75 mu m. To enhance signal-to-noise ratios, we applied a reference-replica topology that can provide the matched input impedance for signal and reference paths in low-noise aimpliers (LNAs). The analog front-end (AFE) consists of LNAs, buffers, programmable gain amplifiers, 10b ADCs, a reference generator, a digital controller, and serial-peripheral interfaces (SPIs). The AFE consumes 51.92 mu W from 1.2 V and 1.8 V supplies in an area of 0.0161 mm(2) per channel, implemented in a 180 nm CMOS process. The AFE shows > 60 dB mid-band CMRR, 6.32 mu V-rms input-referred noise from 0.5 Hz to 10 kHz, and 48 M omega input impedance at 1 kHz. The fabricated AFE chip was directly flip-chip bonded with a 256-channel flexible polyimide neural probe and assembled in a tiny head-stage PCB. Full functionalities of the fabricated 256-channel interface were validated in both in vitro and in vivo experiments, demonstrating the presented hybrid neural recording interface is suitable for various neuroscience studies in the quest of large scale, miniaturized recording systems.11Nsciescopu