Biorobotics/Biomechanics

Spinal cord

Modelling

Neuron

Brain

Analytics

Intracellular

Cerebellum

For three decades our founders challenged the common consensus of one of the biggest scientific questions of our time: How does the brain work?

IntuiCell | Research

Born in the intersection
of AI and Neuroscience.

IntuiCell is a Lund University spin-off with presence in Lund and Stockholm. 

For three decades our founders challenged the common consensus 
of one of the biggest scientific questions of our time:

Today, we apply those groundbreaking neurophysiological insights 
to redesign artificial intelligence. Creating AI that is 

Explore our contrarian research on the mechanisms by which the 
brain predicts the world.

Research

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SE-113 56 Stockholm

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IntuiCell

In vitro studies have revealed intriguing properties of parallel fiber synaptic transmisson. Most notably, these synapses have been shown to induce highly variable synaptic responses, have a pronounced paired pulse facilitation and to induce later, variable synaptic responses in their target neurons. In the present study, whole cell recordings from stellate cells and basket cells were made to evaluate the properties of parallel fiber synaptic transmission under non-anesthetized in vivo conditions in decerebrated cats. Electrical parallel fiber stimulation at threshold intensity was used to study the variability as well as the delayed activation of transmission at single parallel fiber synapses. In addition, the synaptic responses to brief manual skin stimulation, which mimicked the natural synaptic activation pattern and evoked intense spike bursts in these neurons, were analyzed to gain clues about the physiological role of these parallel fiber-specific properties. The data suggest that the high variability pronounced paired-pulse facilitation and the delayed responses reported for parallel fiber synapses in vitro are virtually non-existent in vivo.

In vitro studies have revealed intriguing properties of parallel fiber synaptic transmisson.

Electrophysiological properties of parallel fiber synapses in vivo

In decerebrated, nonanesthetized cats, we made intracellular whole-cell recordings and extracellular cell-attached recordings from granule cells in the cerebellar C3 zone. Spontaneous EPSPs had large, relatively constant peak amplitudes, whereas IPSPs were small and did not appear to contribute substantially to synaptic integration at a short time scale. In many cases, the EPSPs of individual mossy fiber synapses appeared to be separable by their peak amplitudes. A substantial proportion of our granule cells had small receptive fields on the forelimb skin. Skin stimulation evoked explosive responses in which the constituent EPSPs were analyzed. In the rising phase of the response, our analyses indicated a participation of three to four different mossy fiber synapses, corresponding to the total number of mossy fiber afferents. The cutaneous receptive fields of the driven EPSPs overlapped, indicating an absence of convergence of mossy fibers activated from different receptive fields. Also in granule cells activated by joint movements did we find indications that different afferents were driven by the same type of input. Regardless of input type, the temporal patterns of granule cell spike activity, both spontaneous and evoked, appeared to primarily follow the activity in the presynaptic mossy fibers, although much of the nonsynchronized mossy fiber input was filtered out. In contrast to the prevailing theories of granule cell function, our results suggest a function of granule cells as signal-to-noise enhancing threshold elements, rather than as sparse coding pattern discriminators or temporal pattern generators.

In decerebrated, nonanesthetized cats, we made intracellular whole-cell recordings and extracellular cell-attached recordings from granule cells in the cerebellar C3 zone.

Properties of somatosensory synaptic integration in cerebellar granule cells in vivo

Information storage in neural circuits depends on activity-dependent alterations in synaptic weights, such as long-term potentiation (LTP) and long-term depression (LTD). Bidirectional synaptic plasticity endows synapses with mechanisms for rapid reversibility, but it remains unclear how it correlates with reversibility in behavioral learning and whether there is a universal synaptic memory mechanism that operates similarly at all types of synapses. A recently discovered postsynaptic form of LTP at cerebellar parallel fiber (PF)-Purkinje cell (PC) synapses provides a reversal mechanism for PF-LTD and enables a fresh look at the implications of bidirectional plasticity in a brain structure that is particularly suitable to correlate cellular to behavioral learning events. Here, we will review recent studies that reveal unique properties of bidirectional cerebellar plasticity and suggest that the induction cascades for cerebellar LTP and LTD provide a mirror image of their counterparts at hippocampal synapses. We will also discuss how PF-LTP helps to explain reversibility observed in cerebellar motor learning.

Information storage in neural circuits depends on activity-dependent alterations in synaptic weights, such as long-term potentiation (LTP) and long-term depression (LTD).

Synaptic memories upside down: bidirectional plasticity at cerebellar parallel fiber-Purkinje cell synapses

In extracellular recordings, peripheral activation of parallel fiber input in Purkinje cells and interneurons indicates that only a small percentage of parallel fiber synapses are electrically effective. These synapses are all driven from a small receptive field that is specific to the receptive field of the local climbing fiber. This suggests that the synaptic integration performed by these neurons may be much simpler than we generally assume. The scope of the current study was to analyze this synaptic integration using peripheral stimulation.
In cats decerebrated at the intercollicular level, whole-cell patch-clamp recordings in the current clamp mode were obtained from interneurons and somata and dendrites of Purkinje cells in the forelimb area of the C3 zone. Blood pressure, end-expiratory CO2, and body temperature were continuously monitored and maintained within physiologic limits. Patch-clamp electrodes contained 140 mM K-gluconate and 7 mM Cl- as well as other electrolytes. Cells were generally held slightly below (−60 to −80 mV) resting potential to facilitate analysis of synaptic potentials without contaminating spike activity. Synaptic potentials evoked by manual peripheral stimulation and direct electrical stimulation in the inferior olive and in parallel fiber beams were investigated.
In the spontaneous activity of molecular layer interneurons, there are only a few large excitatory postsynaptic potentials (EPSPs). Peripheral stimulation of the receptive field activates many large EPSPs, including the climbing fiber EPSP, as well as inhibitory postsynaptic potentials (IPSPs). Outside the receptive field, few or no postsynaptic potentials are evoked. In Purkinje cell recordings from putative stem dendrites, all-or-nothing calcium spikes are evoked from both the climbing fiber and the parallel fiber receptive fields, but not from any other cutaneous areas. Somatic Purkinje cell recordings are dominated by large excitatory events of various amplitudes. Several characteristics suggest that they are all attenuated calcium spikes generated in stem dendrites.


In extracellular recordings, peripheral activation of parallel fiber input in Purkinje cells and interneurons indicates that only a small percentage of parallel fiber synapses are electrically effective. 

In Vivo Whole-Cell Patch-Clamp Recordings from Purkinje Cells and Interneurons. Synaptic Integration of Peripheral Input

The highly specific relationships between parallel fiber (PF) and climbing fiber (CF) receptive fields in Purkinje cells and interneurons suggest that normal PF receptive fields are established by CF-specific plasticity. To test this idea, we used PF stimulation that was either paired or unpaired with CF activity. Conspicuously, unpaired PF stimulation that induced long-lasting, very large increases in the receptive field sizes of Purkinje cells induced long-lasting decreases in receptive field sizes of their afferent interneurons. In contrast, PF stimulation paired with CF activity that induced long-lasting decreases in the receptive fields of Purkinje cells induced long-lasting, large increases in the receptive fields of interneurons. These properties, and the fact the mossy fiber receptive fields were unchanged, suggest that the receptive field changes were due to bidirectional PF synaptic plasticity in Purkinje cells and interneurons.

The highly specific relationships between parallel fiber (PF) and climbing fiber (CF) receptive fields in Purkinje cells and interneurons suggest that normal PF receptive fields are established by CF-specific plasticity.

Born in the intersection
of AI and Neuroscience.

IntuiCell is a Lund University spin-off with presence in Lund and Stockholm.

For three decades our founders challenged the common consensus
of one of the biggest scientific questions of our time:

How does the brain work?

Today, we apply those groundbreaking neurophysiological insights
to redesign artificial intelligence. Creating AI that is actually intelligent.

Explore our contrarian research on the mechanisms by which the
brain predicts the world.

All Publications.

Born in the intersectionof AI and Neuroscience.

IntuiCell is a Lund University spin-off with presence in Lund and Stockholm.

For three decades our founders challenged the common consensus of one of the biggest scientific questions of our time:

How does the brain work?

Today, we apply those groundbreaking neurophysiological insights to redesign artificial intelligence. Creating AI that is actually intelligent.

Explore our contrarian research on the mechanisms by which the brain predicts the world.

All Publications.

Born in the intersection
of AI and Neuroscience.

For three decades our founders challenged the common consensus
of one of the biggest scientific questions of our time:

Today, we apply those groundbreaking neurophysiological insights
to redesign artificial intelligence. Creating AI that is actually intelligent.

Explore our contrarian research on the mechanisms by which the
brain predicts the world.