Michael Beierlein, Ph.D.

• See Also: Beierlein Lab Website

Mechanisms of Synaptic Plasticity in Neocortical Networks

Neurons in neocortical circuits are interconnected via synapses that can experience dramatic changes in strength during ongoing neuronal activity. How synapses are regulated on a time scale of tens of milliseconds to tens of seconds is not well understood. My laboratory uses electrophysiological and optical recording techniques in mammalian brain slices to explore the mechanisms underlying synaptic plasticity and its importance for local circuit behavior. Ultimately this knowledge will help us to understand the computations performed in neuronal networks that mediate perception, memory formation and higher cognitive functions.

We use the somatosensory cortex of rats and mice as a model system. Here, individual facial whiskers on the animal’s snout map in one-to-one fashion onto anatomically-defined networks of cortical neurons termed barrels. Thalamocortical slices allow for a mechanistic examination of well-defined synaptic pathways, while largely preserving local circuitry which enables more functional studies.

Our initial focus will be on three separate but related questions: We will characterize the dynamic properties of synapses targeting inhibitory interneurons, which will provide insights into the unique role distinct types of interneurons play in controlling circuit activity.

(A) Thalamocortical slice preparation. Arrow indicates barrels in layer 4 of somatosensory cortex. (B) Simultaneous recording of neighboring inhibitory interneurons in cortical layer 4, visualized with IR-DIC optics. (C) Frequency-dependent facilitation. Local excitatory synaptic contact onto inhibitory LTS neuron in layer 4 shows little transmitter release at low frequencies (10 Hz) but displays dramatic short-term facilitation at higher frequencies.

Furthermore, we will study the bidirectional communication between neurons and astrocytes to test whether neocortical astrocytes can regulate transmission of nearby synapses on short time scales, via the release of a ‘gliotransmitter’. Finally, we are interested in the mechanisms and functional consequences of retrograde inhibition mediated by the release of endocannabinoids from different cell types under physiological conditions.

Selected Publications

Gibson, JR, Beierlein, M, Connors, BW. (1999) Two networks of electrically coupled inhibitory neurons in neocortex. Nature 402,75-79.

Beierlein, M, Gibson, JR, Connors, BW. (2000) A network of electrically coupled interneurons drives synchronized inhibition in neocortex. Nat. Neurosci. 3, 904-910.

Beierlein, M, Fall, CP, Rinzel, J, Yuste R. (2002) Thalamocortical bursts trigger recurrent activity in neocortical networks: layer 4 as a frequency-dependent gate. J. Neurosci. 22, 9885-9894.

Beierlein, M, Gibson, JR, Connors, BW. (2003) Two dynamically distinct inhibitory networks in layer 4 of the neocortex. J. Neurophysiol. 90, 2987-3000.

Beierlein, M, Gee, KR, Martin, VV, Regehr, WR. (2004) Presynaptic calcium measurements at physiological temperatures using a new class of dextran-conjugated indicators. J. Neurophysiol. 92, 591-599.

Beierlein, M, Regehr, WG. (2006) Brief bursts of parallel fiber activity trigger calcium waves in Bergmann glia. J. Neurosci. 26, 6958-6967.

Beierlein, M, Regehr, WG. (2006) Local interneurons regulate synaptic strength by retrograde release of endocannabinoids. J. Neurosci. 26, 9935-9943.

Beierlein, M, Fioravante, D, Regehr, WG. (2007) Differential expression of post-tetanic potentiation and retrograde signaling mediate target-dependent short-term synaptic plasticity. Neuron 54(6), 949-959.

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Location & Contact

6431 Fannin Street,
Houston, Texas 77030

PO Box 20708,
Houston, Texas 77225

713.500.4472